Chimeric antigen receptors targeting fc receptor-like 5 and uses thereof

ABSTRACT

The presently disclosed subject matter provides for methods and compositions for treating a neoplasia (e.g., multiple myeloma). It relates to chimeric antigen receptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5), e.g., domain 9 of FcRL5, and immunoresponsive cells comprising such CARs. The presently disclosed FcRL5-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Application SerialNo. PCT/US2015/064134, filed Dec. 4, 2015, which claims priority to U.S.Provisional Patent Application Ser. No. 62/088,164, filed Dec. 5, 2014,the contents of each of which are incorporated by reference in theirentirety, and to each of which priority is claimed.

SEQUENCE LISTING

The specification further incorporates by reference the Sequence Listingsubmitted herewith via EFS on Jun. 5, 2017. Pursuant to 37 C.F.R.§1.52(e)(5), the Sequence Listing text file, identified as0727340295CON_SL.txt, is 1,339,632 bytes and was created on Jun. 5,2017. The Sequence Listing, electronically filed herewith, does notextend beyond the scope of the specification and thus does not containnew matter.

INTRODUCTION

The presently disclosed subject matter provides for methods andcompositions for treating cancer. It relates to chimeric antigenreceptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5),e.g., domain 9 of FcRL5, immunoresponsive cells comprising such CARs,and methods of using such cells for treating cancer (e.g., multiplemyeloma).

BACKGROUND OF THE INVENTION

Cell-based immunotherapy is a therapy with curative potential for thetreatment of cancer. T cells and other immune cells may be modified totarget tumor antigens through the introduction of genetic materialcoding for artificial or synthetic receptors for antigen, termedChimeric Antigen Receptors (CARs), specific to selected antigens.Targeted T cell therapy using CARs has shown recent clinical success intreating hematologic malignancies.

Multiple myeloma (MM) is the second most common hematologic malignancymortality (Siegel et al., CA:a cancer journal for clinicians 63, 11-30(2013)). Approximately 25% of patients have high-risk cytogenetics,which portends a median survival of less then 2 years (Boyd et al.,Genes, chromosomes & cancer 50, 765-774 (2011); Shaughnessy et al.,Blood 109, 2276-2284 (2007)). While recent strides have been made,regardless of cytogenetics, the disease is still considered incurableoutside the immuno-therapeutic graft versus myeloma (GvM) effect of anallogeneic transplant. However, allogeneic transplants are limited byineligibility and high rates of transplant-associated morbidity andmortality (Gahrton et al., The New England journal of medicine 325,1267-1273 (1991)). Similar to the GvM effect, a potentially curative Tcell effect may be achieved with minimal toxicity through autologousadoptive T cell therapy.

Myeloma is expected to be an ideal disease to test adoptive T celltherapy. First, allogeneic transplants demonstrate that the T cell canbe a curative treatment, even with minimal or no concomitantchemotherapy such as after non-myeloablative transplants orpost-transplantation donor lymphocyte infusions. Second, conditioningchemotherapy, possibly through the mechanism of depleting regulatory Tcells (Tregs), enhances the efficacy of adoptive T cell therapy(Brentjens et al., Blood 118, 4817-4828 (2011) and Pegram et al., Blood119, 4133-4141 (2012)) as such, the immediate post-autologous transplantperiod could be an optimal time to administer T cells, and myeloma isone of the few diseases where autologous stem cell transplantation isthe standard of care. Third, the immunomodulatory drug lenalidomide mayimprove CAR based therapy, as has been shown in mice (Bertilaccio etal., Blood 122, 4171 (2013)), and lenalidomide is commonly used to treatMM. Fourth, adoptive T cell therapy works best in bone marrowpredominant disease such as ALL (Brentjens et al., Science translationalmedicine 5, 177ra138 (2013); Davila et al., Science translationalmedicine 6, 224ra225 (2014)), when compared to solid tumors orextra-medullary CLL (Brentjens et al. (2011)) and similar to ALL,myeloma is a disease of the bone marrow.

While there are various reasons to expect that adoptive T cell therapymay work well in MM, expanding adoptive T cell therapy to myeloma posesunique challenges. Unlike other B-cell malignancies, CD19 expression isseen in only 2% of myeloma patients (Bataille et al., Haematologica 91,1234-1240 (2006)). Furthermore, unlike CD19, the common extracellularimmunophenotypic markers in myeloma (CD138, CD38, and CD56) are allco-expressed on other essential cell types, and CARs to any of thesetargets could lead to unacceptable “off tumor, on target” toxicity(Brentjens et al. (2013)) which can be fatal even in targets whereantibodies are well tolerated, as was the case with a HER2 targeted CAR(Morgan et al., Molecular therapy: the journal of the American Societyof Gene Therapy 18, 843-851 (2010)). Accordingly, there are needs fornovel therapeutic strategies to design CARs targeting antigens that arehighly expressed in MM cells and limited expression in normal tissuesfor treating multiple myeloma, which strategies capable of inducingpotent tumor eradication with minimal toxicity and immunogenicity.

SUMMARY OF THE INVENTION

The presently disclosed subject matter generally provides chimericantigen receptors (CARs) that specifically target Fc Receptor-like 5(FcRL5), immunoresponsive cells comprising such CARs, and uses of theseCARs and immunoresponsive cells for treating multiple myeloma.

The presently disclosed subject matter provides CARs. In onenon-limiting example, the CAR comprises an extracellular antigen-bindingdomain, a transmembrane domain and an intracellular domain, where theextracellular antigen-binding domain specifically binds to FcRL5. Incertain embodiments, the extracellular antigen-binding domain binds todomain 9 of FcRL5.

In certain non-limiting embodiments, the extracellular antigen-bindingdomain is a single-chain variable fragment (scFv). In certainembodiments, the extracellular antigen-binding domain is a murine scFv.In certain embodiments, the extracellular antigen-binding domain is ahuman scFv. In certain non-limiting embodiments, the extracellularantigen-binding domain is a Fab, which is optionally crosslinked. Incertain non-limiting embodiments, the extracellular binding domain is aF(ab)₂. In certain non-limiting embodiments, any of the foregoingmolecules can be comprised in a fusion protein with a heterologoussequence to form the extracellular antigen-binding domain. In certainembodiments, the extracellular antigen-binding domain specifically bindsto FcRL5 with a binding affinity (K_(d)) of from about 1×10⁻¹¹ M toabout 3×10⁻⁶M, 1×10⁻¹⁰ M to about 3×10⁻⁶ M or 1×10⁻⁹M to about 3×10⁻⁶ M.In certain embodiments, the extracellular antigen-binding domainspecifically binds to domain 8 or 9 of FcRL5 with a K_(d) of from about1×10⁻⁹M to about 3×10⁻⁶M.

In certain embodiments, the extracellular antigen-binding domaincomprises a light chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:3,SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQID NO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ IDNO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ IDNO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ IDNO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ IDNO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143,SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ IDNO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199,SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ IDNO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255,SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ IDNO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917 and SEQ IDNO:921, wherein the extracellular antigen-binding domain binds to FcRL5.

In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:4,SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQID NO:28, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ IDNO:48, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ IDNO:68, SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ IDNO:88, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ IDNO:108, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQID NO:128, SEQ ID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144,SEQ ID NO:148, SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ IDNO:164, SEQ ID NO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQID NO:184, SEQ ID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200,SEQ ID NO:204, SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ IDNO:220, SEQ ID NO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQID NO:240, SEQ ID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256,SEQ ID NO:260, SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ IDNO:276, SEQ ID NO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQID NO:296, SEQ ID NO:300, SEQ ID NO:304, SEQ ID NO:915 and SEQ IDNO:919, wherein the extracellular antigen-binding domain binds to FcRL5.

In certain embodiments, the extracellular antigen-binding domaincomprises (a) a light chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:3,SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQID NO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ IDNO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ IDNO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ IDNO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ IDNO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143,SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ IDNO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199,SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ IDNO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255,SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ IDNO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917 and SEQ IDNO:921; and (b) a heavy chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:4,SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQID NO:28, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ IDNO:48, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ IDNO:68, SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ IDNO:88, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ IDNO:108, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQID NO:128, SEQ ID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144,SEQ ID NO:148, SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ IDNO:164, SEQ ID NO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQID NO:184, SEQ ID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200,SEQ ID NO:204, SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ IDNO:220, SEQ ID NO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQID NO:240, SEQ ID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256,SEQ ID NO:260, SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ IDNO:276, SEQ ID NO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQID NO:296, SEQ ID NO:300, SEQ ID NO:304, SEQ ID NO:915 and SEQ IDNO:919, wherein the extracellular antigen-binding domain binds to FcRL5.

In certain embodiments, the extracellular antigen-binding domaincomprises a light chain variable region comprising an amino acidsequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:7,SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQ ID NO:27,SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ ID NO:47,SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:67,SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:87,SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:107,SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQ IDNO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143, SEQID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:163,SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQ IDNO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199, SEQID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ ID NO:219,SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQ IDNO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255, SEQID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ ID NO:275,SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQ IDNO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917, SEQ ID NO:921 andconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising an amino acidsequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:8,SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQ ID NO:28,SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ ID NO:48,SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:68,SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88,SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:108,SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQ IDNO:128, SEQ ID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144, SEQID NO:148, SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:164,SEQ ID NO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQ IDNO:184, SEQ ID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200, SEQID NO:204, SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ ID NO:220,SEQ ID NO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQ IDNO:240, SEQ ID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256, SEQID NO:260, SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ ID NO:276,SEQ ID NO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQ IDNO:296, SEQ ID NO:300, SEQ ID NO:304, SEQ ID NO:915, SEQ ID NO:919 andconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:915. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:917. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:919. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:921. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:144. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:143. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:216. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:215. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:220. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:219. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:236. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:235. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:268. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:267. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:116. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:115. In certain embodiments, the extracellular antigen-binding domaincomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:172. In certain embodiments, theextracellular antigen-binding domain comprises a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:171.

In certain embodiments, the extracellular antigen-binding domaincomprises (a) a light chain variable region comprising an amino acidsequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:7,SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQ ID NO:27,SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ ID NO:47,SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:67,SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:87,SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:107,SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQ IDNO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143, SEQID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:163,SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQ IDNO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199, SEQID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ ID NO:219,SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQ IDNO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255, SEQID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ ID NO:275,SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQ IDNO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917, SEQ ID NO:921 andconservative modifications thereof; and (b) a heavy chain variableregion comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:4, SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, SEQID NO:20, SEQ ID NO:24, SEQ ID NO:28, SEQ ID NO:32, SEQ ID NO:36, SEQ IDNO:40, SEQ ID NO:44, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:56, SEQ IDNO:60, SEQ ID NO:64, SEQ ID NO:68, SEQ ID NO:72, SEQ ID NO:76, SEQ IDNO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:92, SEQ ID NO:96, SEQ IDNO:100, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:116, SEQID NO:120, SEQ ID NO:124, SEQ ID NO:128, SEQ ID NO:132, SEQ ID NO:136,SEQ ID NO:140, SEQ ID NO:144, SEQ ID NO:148, SEQ ID NO:152, SEQ IDNO:156, SEQ ID NO:160, SEQ ID NO:164, SEQ ID NO:168, SEQ ID NO:172, SEQID NO:176, SEQ ID NO:180, SEQ ID NO:184, SEQ ID NO:188, SEQ ID NO:192,SEQ ID NO:196, SEQ ID NO:200, SEQ ID NO:204, SEQ ID NO:208, SEQ IDNO:212, SEQ ID NO:216, SEQ ID NO:220, SEQ ID NO:224, SEQ ID NO:228, SEQID NO:232, SEQ ID NO:236, SEQ ID NO:240, SEQ ID NO:244, SEQ ID NO:248,SEQ ID NO:252, SEQ ID NO:256, SEQ ID NO:260, SEQ ID NO:264, SEQ IDNO:268, SEQ ID NO:272, SEQ ID NO:276, SEQ ID NO:280, SEQ ID NO:284, SEQID NO:288, SEQ ID NO:292, SEQ ID NO:296, SEQ ID NO:300, SEQ ID NO:304,SEQ ID NO:915, SEQ ID NO:919 and conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:915; and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:917. In certain embodiments, the extracellular antigen-bindingdomain comprises extracellular antigen-binding domain comprises (a) aheavy chain variable region comprising amino acids having the sequenceset forth in SEQ ID NO:919; and (b) a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:921.In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:144, and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:143. In certain embodiments, the extracellular antigen-bindingdomain comprises (a) a heavy chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:216, and (b) a lightchain variable region comprising amino acids having the sequence setforth in SEQ ID NO:215. In certain embodiments, the extracellularantigen-binding domain comprises (a) a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:220,and (b) a light chain variable region comprising amino acids having thesequence set forth in SEQ ID NO:219. In certain embodiments, theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:236, and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:235. In certainembodiments, the extracellular antigen-binding domain comprises (a) aheavy chain variable region comprising amino acids having the sequenceset forth in SEQ ID NO:268, and (b) a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:267.In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:116, and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:115. In certain embodiments, the extracellular antigen-bindingdomain comprises (a) a heavy chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:172, and (b) a lightchain variable region comprising amino acids having the sequence setforth in SEQ ID NO:171.

In certain non-limiting embodiments, the extracellular antigen-bindingdomain comprises both of said heavy and light chains, optionally with alinker sequence, for example a linker peptide, between the heavy chainvariable region and the light chain variable region. For example, incertain non-limiting embodiments, the extracellular antigen-bindingdomain comprises (a) a heavy chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:915, and (b) a lightchain variable region comprising amino acids having the sequence setforth in SEQ ID NO:917, optionally with (c) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region. In certain embodiments, theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:919 and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:92, optionally with (c)a linker sequence, for example a linker peptide, between the heavy chainvariable region and the light chain variable region. In certainembodiments, the extracellular antigen-binding domain comprises (a) aheavy chain variable region comprising amino acids having the sequenceset forth in SEQ ID NO:144 and (b) a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:143,optionally with (c) a linker sequence, for example a linker peptide,between the heavy chain variable region and the light chain variableregion. In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:216 and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:215, optionally with (c) a linker sequence, for example alinker peptide, between the heavy chain variable region and the lightchain variable region. In certain embodiments, the extracellularantigen-binding domain comprises (a) a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:220and (b) a light chain variable region comprising amino acids having thesequence set forth in SEQ ID NO:219, optionally with (c) a linkersequence, for example a linker peptide, between the heavy chain variableregion and the light chain variable region. In certain embodiments, theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:236 and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:235, optionally with(c) a linker sequence, for example a linker peptide, between the heavychain variable region and the light chain variable region. In certainembodiments, the extracellular antigen-binding domain comprises (a) aheavy chain variable region comprising amino acids having the sequenceset forth in SEQ ID NO:268 and (b) a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:267,optionally with (c) a linker sequence, for example a linker peptide,between the heavy chain variable region and the light chain variableregion. In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:116 and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:115, optionally with (c) a linker sequence, for example alinker peptide, between the heavy chain variable region and the lightchain variable region. In certain embodiments, the extracellularantigen-binding domain comprises (a) a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:172and (b) a light chain variable region comprising amino acids having thesequence set forth in SEQ ID NO:171, optionally with (c) a linkersequence, for example a linker peptide, between the heavy chain variableregion and the light chain variable region.

In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region CDR3 comprising an aminoacid sequence selected from the group consisting of SEQ ID NOs: 311,317, 323, 328, 334, 337, 342, 347, 351, 356, 362, 368, 374, 376, 380,384, 389, 394, 396, 400, 405, 408, 412, 415, 422, 427, 432, 437, 442,446, 451, 453, 456, 458, 459, 463, 464, 467, 473, 476, 482, 486, 489,492, 494, 497, 502, 507, 512, 517, 522, 527, 529, 532, 536, 539, 543,546, 550, 553, 555, 561, 567, 570, 574, 577, 578, 579, 584, 578, 587,591, 925 and 931; and (b) a light chain variable region CDR3 comprisingan amino acid sequence selected from the group consisting of SEQ ID NOs:314, 320, 325, 331, 339, 345, 350, 353, 359, 365, 371, 377, 383, 386,392, 395, 399, 402, 407, 410, 414, 418, 419, 424, 430, 435, 439, 443,449, 452, 455, 457, 462, 465, 470, 479, 485, 488, 491, 493, 495, 499,505, 509, 514, 519, 524, 528, 530, 531, 535, 541, 542, 545, 549, 554,558, 564, 569, 573, 576, 581, 592, 928 and 934.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising an aminoacid sequence selected from the group consisting of SEQ ID NOs: 309,315, 321, 326, 332, 335, 340, 346, 354, 360, 366, 372, 378, 387, 393,403, 411, 420, 425, 436, 440, 444, 471, 480, 500, 510, 515, 520, 525,537, 551, 559, 565, 582, 589, 923 and 929; (b) a heavy chain variableregion CDR2 comprising an amino acid sequence selected from the groupconsisting of SEQ ID NOs: 310, 316, 322, 327, 333, 336, 341, 355, 361,367, 373, 379, 388, 404, 412, 421, 426, 431, 441, 445, 450, 466, 472,475, 481, 496, 501, 506, 511, 516, 521, 526, 538, 552, 560, 566, 583,590, 924 and 930; (c) a heavy chain variable region CDR3 comprising anamino acid sequence selected from the group consisting of SEQ ID NOs:311, 317, 323, 328, 334, 337, 342, 347, 351, 356, 362, 368, 374, 376,380, 384, 389, 394, 396, 400, 405, 408, 412, 415, 422, 427, 432, 437,442, 446, 451, 453, 456, 458, 459, 463, 464, 467, 473, 476, 482, 486,489, 492, 494, 497, 502, 507, 512, 517, 522, 527, 529, 532, 536, 539,543, 546, 550, 553, 555, 561, 567, 570, 574, 577, 578, 579, 584, 578,587, 591, 925 and 931; (d) a light chain variable region CDR1 comprisingan amino acid sequence selected from the group consisting of SEQ ID NOs:312, 318, 324, 329, 338, 343, 348, 352, 357, 363, 369, 381, 390, 397,401, 406, 416, 423, 428, 433, 447, 460, 468, 474, 477, 483, 490, 498,503, 508, 518, 533, 540, 544, 547, 556, 562, 568, 571, 580, 585, 588,926 and 932; (e) a light chain variable region CDR2 comprising an aminoacid sequence selected from the group consisting of SEQ ID NOs: 313,319, 330, 344, 349, 358, 364, 370, 382, 385, 391, 398, 409, 417, 429,434, 438, 448, 454, 461, 469, 478, 484, 487, 504, 513, 523, 534, 429,448, 548, 557, 563, 572, 575, 586, 927 and 933; and (f) a light chainvariable region CDR3 comprising an amino acid sequence selected from thegroup consisting of SEQ ID NOs: 314, 320, 325, 331, 339, 345, 350, 353,359, 365, 371, 377, 383, 386, 392, 395, 399, 402, 407, 410, 414, 418,419, 424, 430, 435, 439, 443, 449, 452, 455, 457, 462, 465, 470, 479,485, 488, 491, 493, 495, 499, 505, 509, 514, 519, 524, 528, 530, 531,535, 541, 542, 545, 549, 554, 558, 564, 569, 573, 576, 581, 592, 928 and934.

In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region CDR1 comprising amino acidshaving the sequence set forth in SEQ ID NO:923 or conservativemodifications thereof, (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:924 orconservative modifications thereof, and (c) a heavy chain variableregion CDR3 comprising amino acids having the sequence set forth in SEQID NO:925 or conservative modifications thereof. In certain embodiments,the extracellular antigen-binding domain comprises (a) a light chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:926 or conservative modifications thereof, (b) alight chain variable region CDR2 comprising amino acids having thesequence set forth in SEQ ID NO:927 or conservative modificationsthereof, and (c) a light chain variable region CDR3 comprising aminoacids having the sequence set forth in SEQ ID NO:928 or conservativemodifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises (a) a heavy chain variable region CDR1 comprising amino acidshaving the sequence set forth in SEQ ID NO:929 or conservativemodifications thereof, (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:930 orconservative modifications thereof, and (c) a heavy chain variableregion CDR3 comprising amino acids having the sequence set forth in SEQID NO:931 or conservative modifications thereof. In certain embodiments,the extracellular antigen-binding domain comprises (a) a light chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:932 or conservative modifications thereof, (b) alight chain variable region CDR2 comprising amino acids having thesequence set forth in SEQ ID NO:933 or conservative modificationsthereof, and (c) a light chain variable region CDR3 comprising aminoacids having the sequence set forth in SEQ ID NO:934 or conservativemodifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising amino acidshaving the sequence set forth in SEQ ID NO:923 or conservativemodifications thereof, (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:924 orconservative modifications thereof, (c) a heavy chain variable regionCDR3 comprising amino acids having the sequence set forth in SEQ IDNO:925 or conservative modifications thereof, (d) a light chain variableregion CDR1 comprising amino acids having the sequence set forth in SEQID NO:926 or conservative modifications thereof, (e) a light chainvariable region CDR2 comprising amino acids having the sequence setforth in SEQ ID NO:927 or conservative modifications thereof, and (f) alight chain variable region CDR3 comprising amino acids having thesequence set forth in SEQ ID NO:928 or conservative modificationsthereof.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising amino acidshaving the sequence set forth in SEQ ID NO:929 or conservativemodifications thereof, (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:930 orconservative modifications thereof, (c) a heavy chain variable regionCDR3 comprising amino acids having the sequence set forth in SEQ IDNO:931 or conservative modifications thereof, (d) a light chain variableregion CDR1 comprising amino acids having the sequence set forth in SEQID NO:932 or conservative modifications thereof, (e) a light chainvariable region CDR2 comprising amino acids having the sequence setforth in SEQ ID NO:933 or conservative modifications thereof, and (f) alight chain variable region CDR3 comprising amino acids having thesequence set forth in SEQ ID NO:934 or conservative modificationsthereof.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:411 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:412 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:463 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:318or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:319 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:419 or conservativemodifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:515 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:516 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:517 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:318or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:319 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:531 or conservativemodifications thereof.

In certain embodiments, the extracellular antigen-binding comprises: (a)a heavy chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:403 or conservative modifications thereof; (b) a heavy chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:404or conservative modifications thereof; (c) a heavy chain variable regionCDR3 comprising the amino acid sequence of SEQ ID NO:532 or conservativemodifications thereof; (d) a light chain variable region CDR1 comprisingthe amino acid sequence of SEQ ID NO:533 or conservative modificationsthereof; (e) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:534 or conservative modifications thereof;and (f) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:535.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:411 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:412 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:543 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:544or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:448 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:545 or conservativemodifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:372 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:475 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:570 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:571thereof; (e) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:572 or conservative modifications thereof;and (f) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:573 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:440 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:441 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:442 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:329or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:330 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:443 or conservativemodifications thereof.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:309 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:310 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:489 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:490or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:313 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:491 or conservativemodifications thereof.

In certain non-limiting embodiments, the extracellular antigen-bindingdomain comprises amino acids having the sequence set forth in SEQ IDNO:664 or conservative modifications thereof. In certain embodiments,the extracellular antigen-binding domain comprises amino acids havingthe sequence set forth in SEQ ID NO:700 or conservative modificationsthereof. In certain embodiments, the extracellular antigen-bindingdomain comprises amino acids having the sequence set forth in SEQ IDNO:702 or conservative modifications thereof. In certain embodiments,the extracellular antigen-binding domain comprises amino acids havingthe sequence set forth in SEQ ID NO:710 or conservative modificationsthereof. In certain embodiments, the extracellular antigen-bindingdomain comprises amino acids having the sequence set forth in SEQ IDNO:726 or conservative modifications thereof. In certain embodiments,the extracellular antigen-binding domain comprises amino acids havingthe sequence set forth in SEQ ID NO:650 or conservative modificationsthereof. In certain embodiments, the extracellular antigen-bindingdomain comprises amino acids having the sequence set forth in SEQ IDNO:678 or conservative modifications thereof.

In certain non-limiting embodiments, the extracellular antigen-bindingdomain comprises (a) a heavy chain variable region CDR1 comprising aminoacids having the sequence set forth in SEQ ID NO:923 or conservativemodifications thereof, a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:924 orconservative modifications thereof, and a heavy chain variable regionCDR3 comprising amino acids having the sequence set forth in SEQ IDNO:925 or conservative modifications thereof, and (ii) a light chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:926 or conservative modifications thereof, a lightchain variable region CDR2 comprising amino acids having the sequenceset forth in SEQ ID NO:927 or conservative modifications thereof, and alight chain variable region CDR3 comprising amino acids having thesequence set forth in SEQ ID NO:928 or conservative modificationsthereof, optionally with (iii) a linker sequence, for example a linkerpeptide, between the heavy chain variable region and the light chainvariable region.

In another non-limiting embodiment, the extracellular antigen-bindingdomain comprises (i) a heavy chain variable region CDR1 comprising aminoacids having the sequence set forth in SEQ ID NO:929 or conservativemodifications thereof, a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:930 orconservative modifications thereof, and a heavy chain variable regionCDR3 comprising amino acids having the sequence set forth in SEQ IDNO:931 or conservative modifications thereof, and (ii) a light chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:932 or conservative modifications thereof, a lightchain variable region CDR2 comprising amino acids having the sequenceset forth in SEQ ID NO:933 or conservative modifications thereof, and alight chain variable region CDR3 comprising amino acids having thesequence set forth in SEQ ID NO:934 or conservative modificationsthereof, optionally with (iii) a linker sequence, for example a linkerpeptide, between the heavy chain variable region and the light chainvariable region.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:411 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:412 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:463 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:318or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:319 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:419 or conservativemodifications thereof, optionally with (g) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:515 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:516 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:517 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:318or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:319 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:531 or conservativemodifications thereof, optionally with (g) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region.

In certain embodiments, the extracellular antigen-binding comprises: (a)a heavy chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:403 or conservative modifications thereof; (b) a heavy chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:404or conservative modifications thereof; (c) a heavy chain variable regionCDR3 comprising the amino acid sequence of SEQ ID NO:532 or conservativemodifications thereof; (d) a light chain variable region CDR1 comprisingthe amino acid sequence of SEQ ID NO:533 or conservative modificationsthereof; (e) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:534 or conservative modifications thereof;and (f) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:535, optionally with (g) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:411 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:412 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:543 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:544or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:448 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:545 or conservativemodifications thereof, optionally with (g) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:372 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:475 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:570 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:571or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:572 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:573 or conservativemodifications thereof, optionally with (g) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:440 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:441 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:442 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:329or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:330 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:443 or conservativemodifications thereof, optionally with (g) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region.

In certain embodiments, the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:309 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:310 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:489 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:490or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:313 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:491 or conservativemodifications thereof, optionally with (g) a linker sequence, forexample a linker peptide, between the heavy chain variable region andthe light chain variable region.

In certain embodiments, the linker peptide comprises an amino acidsequence selected from the group consisting of SEQ ID NO:307 and SEQ IDNO:897.

In certain embodiments, the extracellular antigen-binding domain bindsto FcRL5 comprising the amino acid sequence set forth in SEQ ID NO:899.In certain embodiments, the extracellular antigen-binding domain bindsto an epitope comprising the amino acid sequence set forth in SEQ IDNO:964. In certain embodiments, the extracellular antigen-binding domainbinds to an epitope comprising the amino acid sequence set forth in SEQID NO:965.

In accordance with the presently disclosed subject matter, theextracellular antigen-binding domain is covalently joined to atransmembrane domain. The extracellular antigen-binding domain cancomprise a signal peptide that is covalently joined to the 5′ terminusof the extracellular antigen-binding domain. In certain embodiments, thetransmembrane domain of the CAR comprises a CD8 polypeptide, a CD28polypeptide, a CD3ζ polypeptide, a CD4 polypeptide, a 4-1BB polypeptide,an OX40 polypeptide, an ICOS polypeptide, a CTLA-4 polypeptide, a PD-1polypeptide, a LAG-3 polypeptide, a 2B4 polypeptide, a BTLA polypeptide,a synthetic peptide (not based on a protein associated with the immuneresponse), or a combination thereof. In a non-limiting embodiment, thetransmembrane domain comprises a CD8 polypeptide. In certainembodiments, the transmembrane domain comprises a CD28 polypeptide.

In accordance with the presently disclosed subject matter, in certainembodiments, the intracellular domain comprises a CD3ζ polypeptide. Incertain embodiments, the intracellular domain further comprises at leastone signaling region. In certain embodiments, the at least one signalingregion comprises a CD28 polypeptide, a 4-1BB polypeptide, an OX40polypeptide, an ICOS polypeptide, a DAP-10 polypeptide, a PD-1polypeptide, a CTLA-4 polypeptide, a LAG-3 polypeptide, a 2B4polypeptide, a BTLA polypeptide, a synthetic peptide (not based on aprotein associated with the immune response), or a combination thereof.In certain embodiments, the signaling region is a co-stimulatorysignaling region. In certain embodiments, the co-stimulatory signalingregion comprises a CD28 polypeptide, a 4-1BB polypeptide, an OX40polypeptide, an ICOS polypeptide, a DAP-10 polypeptide, or a combinationthereof. In certain embodiments, the at least one co-stimulatorysignaling region comprises a CD28 polypeptide. In certain non-limitingembodiments, the transmembrane domain comprises a CD28 polypeptide, theintracellular domain comprises a CD3ζ polypeptide, and theco-stimulatory signaling domain comprises a CD28 polypeptide. In certainnon-limiting embodiments, the transmembrane domain comprises a CD8polypeptide, the intracellular domain comprises a CD3ζ polypeptide, andthe co-stimulatory signaling domain comprises a 4-1BB polypeptide.

In certain embodiments, the CAR is recombinantly expressed. The CAR canbe expressed from a vector. In certain embodiments, the vector is aγ-retroviral rector.

The presently disclosed subject matter also provides isolatedimmunoresponsive cells comprising the above-described CARs. In certainembodiments, the isolated immunoresponsive cell is transduced with theCAR, for example, the CAR is constitutively expressed on the surface ofthe immunoresponsive cell. In certain embodiments, the isolatedimmunoresponsive cell is further transduced with at least oneco-stimulatory ligand such that the immunoresponsive cell expresses theat least one co-stimulatory ligand. In certain embodiments, the at leastone co-stimulatory ligand is selected from the group consisting of4-1BBL, CD80, CD86, CD70, OX40L, CD48, TNFRSF14, and combinationsthereof. In certain embodiments, the isolated immunoresponsive cell isfurther transduced with at least one cytokine such that theimmunoresponsive cell secrets the at least one cytokine. In certainembodiments, the at least one cytokine is selected from the groupconsisting of IL-2, IL-3, IL-6, IL-7, IL-11, IL-12, IL-15, IL-17, IL-21,and combinations thereof. In certain embodiments, the isolatedimmunoresponsive cell is selected from the group consisting of a T cell,a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), a regulatoryT cell, a human embryonic stem cell, a lymphoid progenitor cell, a Tcell-precursor cell, and a pluripotent stem cell from which lymphoidcells may be differentiated. In certain embodiments, theimmunoresponsive cell is a T cell.

The presently disclosed subject matter further provides nucleic acidmolecules encoding the presently disclosed CARs, vectors comprising thenucleic acid molecules, and host cells expressing such nucleic acidmolecules. In certain embodiments, the nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:951. In certainembodiments, the nucleic acid molecule comprises nucleic acids havingthe sequence set forth in SEQ ID NO:952. In certain embodiments, thevector is a γ-retroviral vector. In certain embodiments, the host cellis a T cell.

Furthermore, the presently disclosed subject matter provides methods ofusing the above-described immunoresponsive cell for reducing tumorburden in a subject. For example, the presently disclosed subject matterprovides methods of reducing tumor burden in a subject, where the methodcomprises administering an effective amount of the presently disclosedimmunoresponsive cell to the subject, thereby inducing tumor cell deathin the subject. In certain embodiments, the method reduces the number oftumor cells. In another embodiment, the method reduces the tumor size.In yet another embodiment, the method eradicates the tumor in thesubject. In certain embodiments, the tumor is selected from the groupconsisting of multiple myeloma, Non-Hodgkin Lymphoma (especially MantleCell), Hodgkin Lymphoma, Chronic Lymphocytic Leukemia (CLL), Acutelymphocytic leukemia (ALL), Hairy Cell Leukemia, Burketts Lymphoma, andWaldenstrom's Macroglobulinemia. In certain embodiments, the tumor ismultiple myeloma. In certain embodiments, the subject is a human. Incertain embodiments, the immunoresponsive cell is a T cell.

Furthermore, the presently disclosed subject matter provides methods ofusing the above-described immunoresponsive cell for increasing orlengthening survival of a subject having neoplasia. For example, thepresently disclosed subject matter provides methods of increasing orlengthening survival of a subject having neoplasia, where the methodcomprises administering an effective amount of the presently disclosedimmunoresponsive cell to the subject, thereby increasing or lengtheningsurvival of the subject. In certain embodiments, the neoplasia isselected from the group consisting of multiple myeloma, Non-HodgkinLymphoma (especially Mantle Cell), Hodgkin Lymphoma, Chronic LymphocyticLeukemia (CLL), Acute lymphocytic leukemia (ALL), Hairy Cell Leukemia,Burketts Lymphoma, and Waldenstrom's Macroglobulinemia. In certainembodiments, the neoplasia is multiple myeloma. In certain embodiments,the method reduces or eradicates tumor burden in the subject. Thepresently disclosed subject matter also provides methods for producingan immunoresponsive cell that binds to Fc Receptor-like 5 (FcRL5), e.g.,domain 9 of FcRL5. In one non-limiting example, the method comprisesintroducing into the immunoresponsive cell a nucleic acid sequence thatencodes a chimeric antigen receptor (CAR), which comprises anextracellular antigen-binding domain, a transmembrane domain and anintracellular domain, wherein the extracellular antigen-binding domainspecifically binds to Fc Receptor-like 5 (FcRL5). In a specificnon-limiting embodiment, the extracellular antigen-binding domain is anscFv.

The presently disclosed subject matter further provides pharmaceuticalcompositions comprising an effective amount of the presently disclosedimmunoresponsive cells and a pharmaceutically acceptable excipient. Incertain embodiments, the pharmaceutical compositions are for treating aneoplasia. In certain embodiments, the neoplasia is selected from thegroup consisting of multiple myeloma, Non-Hodgkin Lymphoma (especiallyMantle Cell), Hodgkin Lymphoma, Chronic Lymphocytic Leukemia (CLL),Acute lymphocytic leukemia (ALL), Hairy Cell Leukemia, BurkettsLymphoma, and Waldenstrom's Macroglobulinemia. In certain embodiments,the neoplasia is multiple myeloma.

The presently disclosed subject matter further provides kits fortreating a neoplasia, comprising the presently disclosedimmunoresponsive cells. In certain embodiments, the kit further includewritten instructions for using the immunoresponsive cell for treating aneoplasia. In certain embodiments, the neoplasia is selected from thegroup consisting of multiple myeloma, Non-Hodgkin Lymphoma (especiallyMantle Cell), Hodgkin Lymphoma, Chronic Lymphocytic Leukemia (CLL),Acute lymphocytic leukemia (ALL), Hairy Cell Leukemia, BurkettsLymphoma, and Waldenstrom's Macroglobulinemia. In certain embodiments,the neoplasia is multiple myeloma.

BRIEF DESCRIPTION OF THE FIGURES

The following Detailed Description, given by way of example, but notintended to limit the invention to specific embodiments described, maybe understood in conjunction with the accompanying drawings.

FIG. 1 depicts the FcRL5 expression in various normal tissues and humancancer cell lines.

FIG. 2 depicts the screening of anti-FcRL5 scFvs using 3T3 cellsexpressing FcRL5 or FcRL1, 2, 3, 4 or 6.

FIG. 3A-D. (A) A representation of the domains of FcRL5 and the soluble,glycosylphosphatidylinositol (GPI)-anchored and transmembrane forms ofFcRL5. (B) A representation of the vector used to express a mutated formof FcRL5 that lacks domain 9 (also referred to herein as FcRL5Δdom9).(C) The nucleotide sequences of full length FcRL5 and the form of FcRL5that lacks domain 9. (D) A representation of the differences in thenucleotide sequences of full length FcRL5 and the mutated form of FcRL5in which domain 9 is deleted (referred to herein as “FcRL5Δdom9”).

FIG. 4 depicts the screening of anti-FcRL5 scFv ET200-39 on 3T3 cellsexpressing FcRL5Δdom9.

FIG. 5 depicts the screening of anti-FcRL5 scFv ET200-104 on 3T3 cellsexpressing FcRL5Δdom9.

FIG. 6 depicts the screening of anti-FcRL5 scFv ET200-105 on 3T3 cellsexpressing FcRL5Δdom9.

FIG. 7 depicts the screening of anti-FcRL5 scFv ET200-109 on 3T3 cellsexpressing FcRL5Δdom9.

FIG. 8 depicts the screening of anti-FcRL5 scFv ET200-117 on 3T3 cellsexpressing FcRL5Δdom9.

FIGS. 9A-B. Schematics of chimeric antigen receptor targeting FcRL5 inaccordance with non-limiting embodiments of the presently disclosedsubject matter. (A) Schematic of FcRL5-targeted CAR with CD28co-stimulatory domain and CD3zeta. (B) Schematic of FcRL5-targeted CARwith 4-1BB co-stimulatory domain and CD3zeta.

FIG. 10 depicts the vector map of a chimeric antigen receptor targetingFcRL5 using scFV ET200-31 in accordance with one non-limiting embodimentof the presently disclosed subject matter.

FIG. 11 depicts the vector map of a chimeric antigen receptor targetingFcRL5 using scFV ET200-39 in accordance with one non-limiting embodimentof the presently disclosed subject matter.

FIG. 12 depicts the vector map of a chimeric antigen receptor targetingFcRL5 using scFV ET200-69 in accordance with one non-limiting embodimentof the presently disclosed subject matter.

FIG. 13 depicts the vector map of a chimeric antigen receptor targetingFcRL5 using scFV ET200-104 in accordance with one non-limitingembodiment of the presently disclosed subject matter.

FIG. 14 depicts the vector map of a chimeric antigen receptor targetingFcRL5 using scFV ET200-105 in accordance with one non-limitingembodiment of the presently disclosed subject matter.

FIG. 15 depicts the vector map of a chimeric antigen receptor targetingFcRL5 using scFV ET200-109 in accordance with one non-limitingembodiment of the presently disclosed subject matter.

FIG. 16 depicts the vector map of a chimeric antigen receptor targetingFcRL5 using scFV ET200-117 in accordance with one non-limitingembodiment of the presently disclosed subject matter.

FIG. 17 depicts the expression of FcRL5-targeted chimeric antigenreceptors on the surface of transduced T cells.

FIG. 18 depicts the cytotoxicity of FcRL5-targeted chimeric antigenreceptor T cells for FcRL5-expressing cells.

FIG. 19 depicts the induction of cytokine secretion of FcRL5-targetedchimeric antigen receptor T cells.

FIG. 20 depicts the proliferation of FcRL5-targeted chimeric antigenreceptor T cells upon antigen stimulation.

FIG. 21 illustrates the CLIPS technology. The CLIPS reaction takes placebetween bromo groups of the CLIPS scaffold and thiol sidechains ofcysteines. The reaction is fast and specific under mild conditions.Using this elegant chemistry, native protein sequences are transformedinto CLIPS constructs with a range of structures. From left to right:two different single T2 loops, T3 double loop, conjugated T2+T3 loops,stabilized beta sheet, and stabilized alpha helix (Timmerman et al., J.Mol. Recognit. 2007; 20: 283-29).

FIG. 22 illustrates combinatorial clips library screening. The targetprotein (left) containing a discontinuous conformational epitope isconverted into a matrix library (middle). Combinatorial peptides aresynthesized on a proprietary minicard and chemically converted intospatially defined CLIPS constructs (right).

FIG. 23 depicts T3 looped CLIPSTM construct.

FIG. 24A-D illustrates heat map technology. (A) Table of combinedpeptides, with two sub-sequences indicated as “Loop 1” and “Loop 2.” (B)Data from A displayed as a matrix. (C) Color bar indication of the heatmap representation. (D) Heat map visualization of data from A.

FIG. 25 shows heatmap analysis of data recorded for Herceptin.

FIG. 26 shows heatmap analysis of data recorded for ET200-104.

FIG. 27 illustrates a 3D model of amino acid residues 380-731 of FcRL55with peptide stretch ₆₅₇SRPILTFRAPR₆₆₇ highlighted.

DETAILED DESCRIPTION OF THE INVENTION

The presently disclosed subject matter generally provides FcRL5-targetedchimeric antigen receptors (CARs). In one non-limiting example, the CARcomprises an extracellular antigen-binding domain, a transmembranedomain and an intracellular domain, where the extracellularantigen-binding domain specifically binds to FcRL5. In certainembodiments, the extracellular antigen-binding domain specifically bindsto domain 7, 8 or 9 of FcRL5. The presently disclosed subject matteralso provides immunoresponsive cells (e.g., T cell, a Natural Killer(NK) cell, a cytotoxic T lymphocyte (CTL), a regulatory T cell, a humanembryonic stem cell, a lymphoid progenitor cell, a T cell-precursorcell, and a pluripotent stem cell from which lymphoid cells may bedifferentiated) expressing the FcRL5-targeted CARs, and methods of usingsuch immunoresponsive cells for treating a tumor, e.g., multiplemyeloma.

I. Definitions

Unless defined otherwise, all technical and scientific terms used hereinhave the meaning commonly understood by a person skilled in the art towhich this invention belongs. The following references provide one ofskill with a general definition of many of the terms used in thisinvention: Singleton et al., Dictionary of Microbiology and MolecularBiology (2nd ed. 1994); The Cambridge Dictionary of Science andTechnology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R.Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, TheHarper Collins Dictionary of Biology (1991). As used herein, thefollowing terms have the meanings ascribed to them below, unlessspecified otherwise.

As used herein, the term “about” or “approximately” means within anacceptable error range for the particular value as determined by one ofordinary skill in the art, which will depend in part on how the value ismeasured or determined, i.e., the limitations of the measurement system.For example, “about” can mean within 3 or more than 3 standarddeviations, per the practice in the art. Alternatively, “about” can meana range of up to 20%, preferably up to 10%, more preferably up to 5%,and more preferably still up to 1% of a given value. Alternatively,particularly with respect to biological systems or processes, the termcan mean within an order of magnitude, preferably within 5-fold, andmore preferably within 2-fold, of a value.

As used herein, the term “cell population” refers to a group of at leasttwo cells expressing similar or different phenotypes. In non-limitingexamples, a cell population can include at least about 10, at leastabout 100, at least about 200, at least about 300, at least about 400,at least about 500, at least about 600, at least about 700, at leastabout 800, at least about 900, at least about 1000 cells expressingsimilar or different phenotypes.

As used herein, the term “antibody” means not only intact antibodymolecules, but also fragments of antibody molecules that retainimmunogen-binding ability. Such fragments are also well known in the artand are regularly employed both in vitro and in vivo. Accordingly, asused herein, the term “antibody” means not only intact immunoglobulinmolecules but also the well-known active fragments F(ab′)₂, and Fab.F(ab′)₂, and Fab fragments that lack the Fe fragment of intact antibody,clear more rapidly from the circulation, and may have less non-specifictissue binding of an intact antibody (Wahl et al., J. Nucl. Med.24:316-325 (1983). The antibodies of the invention comprise whole nativeantibodies, bispecific antibodies; chimeric antibodies; Fab, Fab′,single chain V region fragments (scFv), fusion polypeptides, andunconventional antibodies.

As used herein, the term “single-chain variable fragment” or “scFv” is afusion protein of the variable regions of the heavy (V_(H)) and lightchains (V_(L)) of an immunoglobulin (e.g., mouse or human) covalentlylinked to form a V_(H)::VL heterodimer. The heavy (V_(H)) and lightchains (V_(L)) are either joined directly or joined by apeptide-encoding linker (e.g., 10, 15, 20, 25 amino acids), whichconnects the N-terminus of the V_(H) with the C-terminus of the V_(L),or the C-terminus of the V_(H) with the N-terminus of the V_(L). Thelinker is usually rich in glycine for flexibility, as well as serine orthreonine for solubility. The linker can link the heavy chain variableregion and the light chain variable region of the extracellularantigen-binding domain. Non-limiting examples of linkers are disclosedin Shen et al., Anal. Chem. 80(6):1910-1917 (2008) and WO 2014/087010,the contents of which are hereby incorporated by reference in theirentireties. In certain embodiments, the linker is a G45 linker.

In a non-limiting example, the linker comprises amino acids having thesequence set forth in SEQ ID NO:897 as provided below. GGGGSGGGGSGGGGS [SEQ ID NO: 897]. In certain embodiments, the nucleic acid sequenceencoding the amino acid sequence of SEQ ID NO:897 is set forth in SEQ IDNO:898, which is provided below:GGTGGAGGTGGATCAGGTGGAGGTGGATCTGGTGGAGGTGGATCT [SEQ ID NO:898].

In another non-limiting example, the linker comprises amino acids havingthe sequence set forth in SEQ ID NO:307 as provided below:SRGGGGSGGGGSGGGGSLEMA [SEQ ID No: 307]. In certain embodiments, thenucleic acid sequence encoding the amino acid sequence of SEQ ID NO:307is set forth in SEQ ID NO:305, which is provided below:

[SEQ ID NO: 305] TCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCC.

Despite removal of the constant regions and the introduction of alinker, scFv proteins retain the specificity of the originalimmunoglobulin. Single chain Fv polypeptide antibodies can be expressedfrom a nucleic acid comprising V_(H)- and V_(L)-encoding sequences asdescribed by Huston, et al. (Proc. Nat. Acad. Sci. USA, 85:5879-5883,1988). See, also, U.S. Pat. Nos. 5,091,513, 5,132,405 and 4,956,778; andU.S. Patent Publication Nos. 20050196754 and 20050196754. AntagonisticscFvs having inhibitory activity have been described (see, e.g., Zhao etal., Hyrbidoma (Larchmt) 2008 27(6):455-51; Peter et al., J CachexiaSarcopenia Muscle 2012 August 12; Shieh et al., J Imunol 2009183(4):2277-85; Giomarelli et al., Thromb Haemost 2007 97(6):955-63;Fife eta., J Clin Invst 2006 116(8):2252-61; Brocks et al.,Immunotechnology 1997 3(3):173-84; Moosmayer et al., Ther Immunol 19952(10:31-40). Agonistic scFvs having stimulatory activity have beendescribed (see, e.g., Peter et al., J Bioi Chem 2003 25278(38):36740-7;Xie et al., Nat Biotech 1997 15(8):768-71; Ledbetter et al., Crit RevImmunol 1997 17(5-6):427-55; Ho et al., BioChim Biophys Acta 20031638(3):257-66).

As used herein, “F(ab)” refers to a fragment of an antibody structurethat binds to an antigen but is monovalent and does not have a Fcportion, for example, an antibody digested by the enzyme papain yieldstwo F(ab) fragments and an Fc fragment (e.g., a heavy (H) chain constantregion; Fc region that does not bind to an antigen).

As used herein, “F(ab′)₂” refers to an antibody fragment generated bypepsin digestion of whole IgG antibodies, wherein this fragment has twoantigen binding (ab′) (bivalent) regions, wherein each (ab′) regioncomprises two separate amino acid chains, a part of a H chain and alight (L) chain linked by an S—S bond for binding an antigen and wherethe remaining H chain portions are linked together. A “F(ab′)₂” fragmentcan be split into two individual Fab′ fragments.

As used herein, the term “vector” refers to any genetic element, such asa plasmid, phage, transposon, cosmid, chromosome, virus, virion, etc.,which is capable of replication when associated with the proper controlelements and which can transfer gene sequences into cells. Thus, theterm includes cloning and expression vehicles, as well as viral vectorsand plasmid vectors.

As used herein, the term “expression vector” refers to a recombinantnucleic acid sequence, i.e., recombinant DNA molecule, containing adesired coding sequence and appropriate nucleic acid sequences necessaryfor the expression of the operably linked coding sequence in aparticular host organism. Nucleic acid sequences necessary forexpression in prokaryotes usually include a promoter, an operator(optional), and a ribosome binding site, often along with othersequences. Eukaryotic cells are known to utilize promoters, enhancers,and termination and polyadenylation signals.

As used herein, “CDRs” are defined as the complementarity determiningregion amino acid sequences of an antibody which are the hypervariableregions of immunoglobulin heavy and light chains. See, e.g., Kabat etal., Sequences of Proteins of Immunological Interest, 4th U. S.Department of Health and Human Services, National Institutes of Health(1987). Generally, antibodies comprise three heavy chain and three lightchain CDRs or CDR regions in the variable region. CDRs provide themajority of contact residues for the binding of the antibody to theantigen or epitope. In certain embodiments, the CDRs regions aredelineated using the Kabat system (Kabat, E. A., et al. (1991) Sequencesof Proteins of Immunological Interest, Fifth Edition, U.S. Department ofHealth and Human Services, NIH Publication No. 91-3242).

As used herein, the term “affinity” is meant a measure of bindingstrength. Without being bound to theory, affinity depends on thecloseness of stereochemical fit between antibody combining sites andantigen determinants, on the size of the area of contact between them,and on the distribution of charged and hydrophobic groups. Affinity alsoincludes the term “avidity,” which refers to the strength of theantigen-antibody bond after formation of reversible complexes. Methodsfor calculating the affinity of an antibody for an antigen are known inthe art, comprising use of binding experiments to calculate affinity.Antibody activity in functional assays (e.g., flow cytometry assay) isalso reflective of antibody affinity. Antibodies and affinities can bephenotypically characterized and compared using functional assays (e.g.,flow cytometry assay).

Nucleic acid molecules useful in the methods of the invention includeany nucleic acid molecule that encodes a polypeptide of the invention ora fragment thereof. Such nucleic acid molecules need not be 100%identical with an endogenous nucleic acid sequence, but will typicallyexhibit substantial identity. Polynucleotides having “substantialidentity” to an endogenous sequence are typically capable of hybridizingwith at least one strand of a double-stranded nucleic acid molecule. By“hybridize” is meant pair to form a double-stranded molecule betweencomplementary polynucleotide sequences (e.g., a gene described herein),or portions thereof, under various conditions of stringency. (See, e.g.,Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399; Kimmel, A.R. (1987) Methods Enzymol. 152:507).

For example, stringent salt concentration will ordinarily be less thanabout 750 mM NaCl and 75 mM trisodium citrate, preferably less thanabout 500 mM NaCl and 50 mM trisodium citrate, and more preferably lessthan about 250 mM NaCl and 25 mM trisodium citrate. Low stringencyhybridization can be obtained in the absence of organic solvent, e.g.,formamide, while high stringency hybridization can be obtained in thepresence of at least about 35% formamide, and more preferably at leastabout 50% formamide. Stringent temperature conditions will ordinarilyinclude temperatures of at least about 30° C., more preferably of atleast about 37° C., and most preferably of at least about 42° C. Varyingadditional parameters, such as hybridization time, the concentration ofdetergent, e.g., sodium dodecyl sulfate (SDS), and the inclusion orexclusion of carrier DNA, are well known to those skilled in the art.Various levels of stringency are accomplished by combining these variousconditions as needed. In a preferred: embodiment, hybridization willoccur at 30° C. in 750 mM NaCl, 75 mM trisodium citrate, and 1% SDS. Ina more preferred embodiment, hybridization will occur at 37° C. in 500mM NaCl, 50 mM trisodium citrate, 1% SDS, 35% formamide, and 100 μg/mldenatured salmon sperm DNA (ssDNA). In a most preferred embodiment,hybridization will occur at 42° C. in 250 mM NaCl, 25 mM trisodiumcitrate, 1% SDS, 50% formamide, and 200 μg/ml ssDNA. Useful variationson these conditions will be readily apparent to those skilled in theart.

For most applications, washing steps that follow hybridization will alsovary in stringency. Wash stringency conditions can be defined by saltconcentration and by temperature. As above, wash stringency can beincreased by decreasing salt concentration or by increasing temperature.For example, stringent salt concentration for the wash steps willpreferably be less than about 30 mM NaCl and 3 mM trisodium citrate, andmost preferably less than about 15 mM NaCl and 1.5 mM trisodium citrate.Stringent temperature conditions for the wash steps will ordinarilyinclude a temperature of at least about 25° C., more preferably of atleast about 42° C., and even more preferably of at least about 68° C. Ina preferred embodiment, wash steps will occur at 25° C. in 30 mM NaCl, 3mM trisodium citrate, and 0.1% SDS. In a more preferred embodiment, washsteps will occur at 42° C. in 15 mM NaCl, 1.5 mM trisodium citrate, and0.1% SDS. In a more preferred embodiment, wash steps will occur at 68°C. in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. Additionalvariations on these conditions will be readily apparent to those skilledin the art. Hybridization techniques are well known to those skilled inthe art and are described, for example, in Benton and Davis (Science196:180, 1977); Grunstein and Rogness (Proc. Natl. Acad. Sci., USA72:3961, 1975); Ausubel et al. (Current Protocols in Molecular Biology,Wiley Interscience, New York, 2001); Berger and Kimmel (Guide toMolecular Cloning Techniques, 1987, Academic Press, New York); andSambrook et al., Molecular Cloning: A Laboratory Manual, Cold SpringHarbor Laboratory Press, New York.

By “substantially identical” is meant a polypeptide or nucleic acidmolecule exhibiting at least 50% identity to a reference amino acidsequence (for example, any one of the amino acid sequences describedherein) or nucleic acid sequence (for example, any one of the nucleicacid sequences described herein). Preferably, such a sequence is atleast 60%, more preferably 80% or 85%, and more preferably 90%, 95% oreven 99% identical at the amino acid level or nucleic acid to thesequence used for comparison.

Sequence identity is typically measured using sequence analysis software(for example, Sequence Analysis Software Package of the GeneticsComputer Group, University of Wisconsin Biotechnology Center, 1710University Avenue, Madison, Wis. 53705, BLAST, BESTFIT, GAP, orPILEUP/PRETTYBOX programs). Such software matches identical or similarsequences by assigning degrees of homology to various substitutions,deletions, and/or other modifications. In an exemplary approach todetermining the degree of identity, a BLAST program may be used, with aprobability score between e-3 and e-100 indicating a closely relatedsequence.

As used herein, the term “analog” refers to a structurally relatedpolypeptide or nucleic acid molecule having the function of a referencepolypeptide or nucleic acid molecule.

As used herein, the term “ligand” refers to a molecule that binds to areceptor. In particular, the ligand binds a receptor on another cell,allowing for cell-to-cell recognition and/or interaction.

As used herein, the term “disease” refers to any condition or disorderthat damages or interferes with the normal function of a cell, tissue,or organ. Examples of diseases include neoplasia or pathogen infectionof cell.

As used herein, the term “effective amount” refers to an amountsufficient to have a therapeutic effect. In certain embodiments, an“effective amount” is an amount sufficient to arrest, ameliorate, orinhibit the continued proliferation, growth, or metastasis (e.g.,invasion, or migration) of a neoplasia.

As used herein, the term “heterologous nucleic acid molecule orpolypeptide” refers to a nucleic acid molecule (e.g., a cDNA, DNA or RNAmolecule) or polypeptide that is not normally present in a cell orsample obtained from a cell. This nucleic acid may be from anotherorganism, or it may be, for example, an mRNA molecule that is notnormally expressed in a cell or sample.

As used herein, the term “immunoresponsive cell” refers to a cell thatfunctions in an immune response or a progenitor, or progeny thereof.

As used herein, the term “modulate” refers positively or negativelyalter. Exemplary modulations include an about 1%, about 2%, about 5%,about 10%, about 25%, about 50%, about 75%, or about 100% change.

As used herein, the term “increase” refers to alter positively by atleast about 5%, including, but not limited to, alter positively by about5%, by about 10%, by about 25%, by about 30%, by about 50%, by about75%, or by about 100%.

As used herein, the term “reduce” refers to alter negatively by at leastabout 5% including, but not limited to, alter negatively by about 5%, byabout 10%, by about 25%, by about 30%, by about 50%, by about 75%, or byabout 100%.

As used herein, the term “isolated cell” refers to a cell that isseparated from the molecular and/or cellular components that naturallyaccompany the cell.

As used herein, the term “isolated,” “purified,” or “biologically pure”refers to material that is free to varying degrees from components whichnormally accompany it as found in its native state. “Isolate” denotes adegree of separation from original source or surroundings. “Purify”denotes a degree of separation that is higher than isolation. A“purified” or “biologically pure” protein is sufficiently free of othermaterials such that any impurities do not materially affect thebiological properties of the protein or cause other adverseconsequences. That is, a nucleic acid or peptide of this invention ispurified if it is substantially free of cellular material, viralmaterial, or culture medium when produced by recombinant DNA techniques,or chemical precursors or other chemicals when chemically synthesized.Purity and homogeneity are typically determined using analyticalchemistry techniques, for example, polyacrylamide gel electrophoresis orhigh performance liquid chromatography. The term “purified” can denotethat a nucleic acid or protein gives rise to essentially one band in anelectrophoretic gel. For a protein that can be subjected tomodifications, for example, phosphorylation or glycosylation, differentmodifications may give rise to different isolated proteins, which can beseparately purified.

As used herein, the term “secreted” is meant a polypeptide that isreleased from a cell via the secretory pathway through the endoplasmicreticulum, Golgi apparatus, and as a vesicle that transiently fuses atthe cell plasma membrane, releasing the proteins outside of the cell.

As used herein, the term “specifically binds” or “specifically binds to”or “specifically target” is meant a polypeptide or fragment thereof thatrecognizes and binds a biological molecule of interest (e.g., apolypeptide), but which does not substantially recognize and bind othermolecules in a sample, for example, a biological sample, which naturallyincludes a polypeptide of the invention.

As used herein, the term “treating” or “treatment” refers to clinicalintervention in an attempt to alter the disease course of the individualor cell being treated, and can be performed either for prophylaxis orduring the course of clinical pathology. Therapeutic effects oftreatment include, without limitation, preventing occurrence orrecurrence of disease, alleviation of symptoms, diminishment of anydirect or indirect pathological consequences of the disease, preventingmetastases, decreasing the rate of disease progression, amelioration orpalliation of the disease state, and remission or improved prognosis. Bypreventing progression of a disease or disorder, a treatment can preventdeterioration due to a disorder in an affected or diagnosed subject or asubject suspected of having the disorder, but also a treatment mayprevent the onset of the disorder or a symptom of the disorder in asubject at risk for the disorder or suspected of having the disorder.

As used herein, the term “subject” refers to any animal (e.g., amammal), including, but not limited to, humans, non-human primates,rodents, and the like (e.g., which is to be the recipient of aparticular treatment, or from whom cells are harvested).

II. Fc Receptor-Like 5 (FcRL5)

Fc Receptor-Like 5 (FcRL5) (also known as “CD307e” or “IRTA2”) is arational target for treating multiple myeloma as it is expressed on Bcells and plasma cells. FcRL5 binds to the Fc portion of IgG andcontributes to B cell receptor signaling and B cell proliferation(Franco et al., Journal of immunology 190, 5739-5746 (2013);Dement-Brown et al., Journal of leukocyte biology 91, 59-67 (2012).FcRL5 was found to be an alternative to CD138 as a FACS marker formalignant plasma cells from fresh or frozen patient samples with a meanrelative MFI between 10-55 (n=23) (Ise et al., Leukemia 21, 169-174(2007)). Another study confirmed cell surface expression of FcRL5 byFACS on primary patient samples from most chronic lymphocytic leukemia(CLL), and mantle cell lymphoma cases, and all multiple myeloma (MM)(n=8) cases tested (Ise et al. (2007)). A third group found high surfacestaining on plasma cells from normal bone marrows (n=7), in MGUS (n=16),and in MM (n=16), (MFI similar in all three groups, ˜1000 fold increasecompared to isotype control) (Elkins et al., Molecular cancertherapeutics 11, 2222-2232 (2012)). FcRL5 is on 1q21 and has been foundto be involved in 1q21 abnormalities in B cell malignancies(Hatzivassiliou et al., Immunity 14, 277-289 (2001)). Amplification of1q21 is found in 48% of MM patients at diagnosis and 67% of patients atrelapse, and correlates with a worse prognosis (An et al., Haematologica99, 353-359 (2014)). An antibody-drug conjugate targeting FcRL5 waseffective in treating an in vivo murine model of MM (Elkins et al.(2012)).

Non-limiting examples of human FcRL5 amino acid sequences can be foundunder GenBank Protein Accession Nos: AAI01070.1; XP_011508332.1;XP_011508334.1; XP_011508333.1; XP_011508332.1; and NP_001182317.1.

In certain non-limiting embodiments, FcRL5 is human FcRL5 having theamino acid sequence set forth in SEQ ID NO:899, or fragments thereof.SEQ ID NO:899 is provided below:

[SEQ ID NO: 899] MLLWVILLVLAPVSGQFARTPRPIIFLQPPWTTVFQGERVTLTCKGFRFYSPQKTKWYHRYLGKEILRETPDNILEVQESGEYRCQAQGSPLSSPVHLDFSSASLILQAPLSVFEGDSVVLRCRAKAEVTLNNTIYKNDNVLAFLNKRTDFHIPHACLKDNGAYRCTGYKESCCPVSSNTVKIQVQEPFTRPVLRASSFQPISGNPVTLTCETQLSLERSDVPLRFRFFRDDQTLGLGWSLSPNFQITAMWSKDSGFYWCKAATMPHSIISDSPRSWIQVQIPASHPVLTLSPEKALNFEGTKVTLHCETQEDSLRTLYRFYHEGVPLRHKSVRCERGASISFSLTTENSGNYYCTADNGLGAKPSKAVSLSVTVPVSHPVLNLSSPEDLIFEGAKVTLHCEAQRGSLPILYQFHHEDAALERRSANSAGGVAISFSLTAEHSGNYYCTADNGFGPQRSKAVSLSITVPVSHPVLTLSSAEALTFEGATVTLHCEVQRGSPQILYQFYHEDMPLWSSSTPSVGRVSFSFSLTEGHSGNYYCTADNGFGPQRSEVVSLFVTVPVSRPILTLRVPRAQAVVGDLLELHCEAPRGSPPILYWFYHEDVTLGSSSAPSGGEASFNLSLTAEHSGNYSCEANNGLVAQHSDTISLSVIVPVSRPILTFRAPRAQAVVGDLLELHCEALRGSSPILYWFYHEDVTLGKISAPSGGGASFNLSLTTEHSGIYSCEADNGLEAQRSEMVTLKVAVPVSRPVLTLRAPGTHAAVGDLLELHCEALRGSPLILYRFFHEDVTLGNRSSPSGGASLNLSLTAEHSGNYSCEADNGLGAQRSETVTLYITGLTANRSGPFATGVAGGLLSIAGLAAGALLLYCWLSRKAGRKPASDPARSPSDSDSQEPTYHNVPAWEELQPVYTNANPRGENVVYSEVRIIQEKKKHAVASDPRHLRNKGSPIIYSEVKVASTPVSGSLFLASSAPHR.

In certain embodiments, FcRL5 comprises 9 immunoglobulin (Ig)-likedomains, e.g., domain 1, domain 2, domain 3, domain 4, domain 5, domain6, domain 7, domain 8 and domain 9 (see FIGS. 3A and 3C). In certainembodiments, domain 9 of FcRL5 comprises the amino acid sequence setforth in SEQ ID NO:900. SEQ ID NO:900 is provided below.

[SEQ ID NO: 900] RPVLTLRAPGTHAAVGDLLELHCEALRGSPLILYRFFHEDVTLGNRSSPSGGASLNLSLTAEHSGNYSCEADNGLGAQRSETVTLYI.

In certain embodiments, domain 9 of FcRL5 can have the amino acidsequence set forth in SEQ ID NO:963, or fragments thereof. SEQ ID NO:963is provided below:

[SEQ ID NO: 963] GTHAAVGDLLELHCEALRGSPLILYRFFHEDVTLGNRSSPSGGASLNLSLTAEHSGNYSCEADNGLGAQRSETVTLYI.

In certain embodiments, domain 1 can comprise amino acids 23-100 of SEQID NO:899; domain 2 can comprise amino acids 105-185 of SEQ ID NO:899;domain 3 can comprise amino acids 191-273 of SEQ ID NO:899; domain 4 cancomprise amino acids 287-373 of SEQ ID NO:899; domain 5 can compriseamino acids 380-466 of SEQ ID NO:899; domain 6 can comprise amino acids490-555 of SEQ ID NO:899; domain 7 can comprise amino acids 565-638 ofSEQ ID NO:899; domain 8 can comprise amino acids 658-731 of SEQ IDNO:899; and domain 9 can comprise amino acids 754-835 of SEQ ID NO:899.

In certain embodiments, domain 9 of FcRL5 comprises an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous tothe amino acid sequence of SEQ ID NO:900 or 963.

III. Chimeric Antigen Receptor (CAR)

Chimeric antigen receptors (CARs) are engineered receptors, which graftor confer a specificity of interest onto an immune effector cell. CARscan be used to graft the specificity of a monoclonal antibody onto a Tcell; with transfer of their coding sequence facilitated by retroviralvectors.

There are three generations of CARs. “First generation” CARs aretypically composed of an extracellular antigen binding domain (e.g., asingle-chain variable fragments (scFv)) fused to a transmembrane domain,fused to cytoplasmic/intracellular domain of the T cell receptor chain.“First generation” CARs typically have the intracellular domain from theCD3ζ-chain, which is the primary transmitter of signals from endogenousTCRs. “First generation” CARs can provide de novo antigen recognitionand cause activation of both CD4⁺ and CD8⁺ T cells through their CD3ζchain signaling domain in a single fusion molecule, independent ofHLA-mediated antigen presentation. “Second generation” CARs addintracellular domains from various co-stimulatory molecules (e.g., CD28,4-1BB, ICOS, OX40) to the cytoplasmic tail of the CAR to provideadditional signals to the T cell. “Second generation” CARs comprisethose that provide both co-stimulation (e.g., CD28 or 4-1BB) andactivation (CD3ζ). Preclinical studies have indicated that “SecondGeneration” CARs can improve the anti-tumor activity of T cells. Forexample, robust efficacy of “Second Generation” CAR modified T cells wasdemonstrated in clinical trials targeting the CD19 molecule in patientswith chronic lymphoblastic leukemia (CLL) and acute lymphoblasticleukemia (ALL). “Third generation” CARs comprise those that providemultiple co-stimulation (e.g., CD28 and 4-1BB) and activation (CD3ζ).

In accordance with the presently disclosed subject matter, the CARscomprise an extracellular antigen-binding domain, a transmembrane domainand an intracellular domain, where the extracellular antigen-bindingdomain binds to FcRL5. In a specific non-limiting embodiment, theextracellular antigen-binding domain is a scFv. In a specificnon-limiting embodiment, the extracellular antigen-binding domain is aFab, which is optionally crosslinked. In a specific non-limitingembodiment, the extracellular binding domain is a F(ab)₂. In a specificnon-limiting embodiment, any of the foregoing molecules may be comprisedin a fusion protein with a heterologous sequence to form theextracellular antigen-binding domain.

In certain non-limiting embodiments, the extracellular antigen-bindingdomain of a CAR of the present disclosure has a high binding specificityas well as high binding affinity to FcRL5 or domain 9 of FcRL5. Incertain non-limiting embodiments, the extracellular antigen-bindingdomain of a CAR of the present disclosure has a high binding specificityas well as high binding affinity to domain 8 of FcRL5. In certainnon-limiting embodiments, the extracellular antigen-binding domain of aCAR of the present disclosure has a high binding specificity as well ashigh binding affinity to domain 7 of FcRL5. For example, in suchembodiments, the extracellular antigen-binding domain of the CAR(embodied, for example, in an scFv or an analog thereof) binds to FcRL5(or domain 8 or domain 9 of FcRL5) with a dissociation constant (K_(d))of about 3×10⁻⁶ M or less. In certain embodiments, the K_(d) is about1×10⁻⁶ M or less, about 1×10⁻⁷ M or less, about 1×10⁻⁸ M or less, about1×10⁻⁹ M or less, about 1×10⁻¹⁰ M or less or about 1×10⁻¹¹ M or less. Incertain embodiments, the K_(d) is from about 1×10⁻¹¹ M to about 3×10⁻⁶M, 1×10⁻¹⁰ M to about 3×10⁻⁶ M or from about 1×10⁻⁹M to about 3×10⁻⁶ M,such as from about 1×10⁻⁹M to about 1×10⁻⁸ M, from about 1×10⁻⁸M toabout 1×10⁻⁷ M, or from about 1×10⁻⁷M to about 1×10⁻⁶ M, or from about1×10⁻⁶ M to about 3×10⁻⁶ M.

Binding of the extracellular antigen-binding domain (embodiment, forexample, in an scFv or an analog thereof) of a presently disclosed CARto FcRL5 (or domain 8 or domain 9 of FcRL5) can be confirmed by, forexample, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay(RIA), FACS analysis, bioassay (e.g., growth inhibition), or WesternBlot assay. Each of these assays generally detect the presence ofprotein-antibody complexes of particular interest by employing a labeledreagent (e.g., an antibody, or an scFv) specific for the complex ofinterest. For example, the scFv can be radioactively labeled and used ina radioimmunoassay (RIA) (see, for example, Weintraub, B., Principles ofRadioimmunoassays, Seventh Training Course on Radioligand AssayTechniques, The Endocrine Society, March, 1986, which is incorporated byreference herein). The radioactive isotope can be detected by such meansas the use of a γ counter or a scintillation counter or byautoradiography. In certain embodiments, the FcRL5-targetedextracellular antigen-binding domain is labeled with a fluorescentmarker. Non-limiting examples of fluorescent markers include greenfluorescent protein (GFP), blue fluorescent protein (e.g., EBFP, EBFP2,Azurite, and mKalamal), cyan fluorescent protein (e.g., ECFP, Cerulean,and CyPet), and yellow fluorescent protein (e.g., YFP, Citrine, Venus,and YPet). In certain embodiments, the FcRL5-targeted human scFv islabeled with GFP.

In certain embodiments, the extracellular antigen-binding domain of apresently disclosed CAR comprises a single-chain variable fragment(scFv). In one specific embodiment, the extracellular antigen-bindingdomain of a presently disclosed CAR comprises a human scFv thatspecifically binds to human FcRL5. In another specific embodiment, theextracellular antigen-binding domain of a presently disclosed CARcomprises a murine scFv that specifically binds to human FcRL5. Incertain embodiments, the extracellular antigen-binding domain of apresently disclosed CAR comprises a scFv that specifically binds to atleast a portion of domain 7 of FcRL5. In certain embodiments, theextracellular antigen-binding domain of a presently disclosed CARcomprises a scFv that specifically binds to at least a portion of domain8 of FcRL5. In certain embodiments, the extracellular antigen-bindingdomain of a presently disclosed CAR comprises a scFv that specificallybinds to at least a portion of domain 9 of FcRL5. For example, and notby way of limitation, domain 9 of FcRL5 comprises the amino acidsequence set forth in SEQ ID NO:900 or 963, or fragments thereof.

In certain embodiments, the extracellular antigen-binding domain is amurine scFv obtained from two commercially available mouse hybridomasbinding different extracellular epitopes on human FcRL5, which have beencharacterized in the Franco et al., Journal of Immunology (2013);190:5739-5746; Ise et al., Clinical cancer research: an official fournalof the American Association for Cancer Research (2005); 11:87-96; andIse et al., Clinical chemistry and laboratory medicine: CCLM/FESCC(2006); 44:594-602, each of which are herein incorporated by referencein their entireties. In certain embodiments, the extracellularantigen-binding domain is a murine scFv that is derived from a heavychain variable region and a light chain variable region of an antibodythat binds to human FcRL5, e.g., antibodies F56 and F119 as disclosed inIse et al. (2005), which is herein incorporated by reference in itsentirety.

Extracellular Antigen-Binding Domain of A CAR

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising an amino acidsequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:7,SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQ ID NO:27,SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ ID NO:47,SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:67,SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:87,SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:107,SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQ IDNO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143, SEQID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:163,SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQ IDNO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199, SEQID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ ID NO:219,SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQ IDNO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255, SEQID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ ID NO:275,SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQ IDNO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917 and SEQ ID NO:921,wherein the scFv antibody binds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising an amino acidsequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:8,SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQ ID NO:28,SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ ID NO:48,SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:68,SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88,SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:108,SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQ IDNO:128, SEQ ID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144, SEQID NO:148, SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:164,SEQ ID NO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQ IDNO:184, SEQ ID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200, SEQID NO:204, SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ ID NO:220,SEQ ID NO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQ IDNO:240, SEQ ID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256, SEQID NO:260, SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ ID NO:276,SEQ ID NO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQ IDNO:296, SEQ ID NO:300, SEQ ID NO:304, SEQ ID NO:915 and SEQ ID NO:919.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:915 as provided below.

[SEQ ID NO: 915] VKLQESGGGLVQPGGSRKLSCAASGFTFSIFGLHWVRQAPEKGLEWVAYISGDSNTIYYADTVKGRFTISRDNPKNTLFLQMTSLRSEDTAMYYCARNSY YALDYWGQGTTVTVSS

The nucleic acid sequence encoding the amino acid sequence of SEQ IDNO:915 is set forth in SEQ ID NO:916 as provided below.

[SEQ ID NO: 916] GTGAAGCTGCAGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCGGAAACTCTCCTGTGCAGCCTCTGGATTCACTTTCAGTATCTTTGGATTGCACTGGGTTCGTCAGGCTCCAGAGAAGGGGCTGGAGTGGGTCGCATACATTAGTGGTGACAGTAATACCATCTACTATGCAGACACAGTGAAGGGCCGATTCACCATCTCCAGAGACAATCCCAAGAACACCCTGTTCCTGCAAATGACCAGTCTAAGGTCTGAGGACACGGCCATGTATTACTGTGCAAGAAATAGCTACTATGCTCTGGACTACTGGGGCCAAGGGACCACGGTCACCGTCTCCTCA

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:917 as provided below.

[SEQ ID NO: 917] DIELTQSPAIMSVSPGEKVTMTCRASSSVSSSYLHWYQQRSGASPKIWIYSTSNLASGVPARFSGSGTGTSYSLTISSVEAEDAATYYCQQYSGYPWTFG GGTKLEI

The nucleic acid sequence encoding the amino acid sequence of SEQ IDNO:917 is set forth in SEQ ID NO:918 as provided below.

[SEQ ID NO: 918] GACATTGAGCTCACCCAGTCTCCAGCAATCATGTCTGTATCTCCAGGTGAAAAGGTCACCATGACCTGCAGGGCCAGCTCAAGTGTCAGTTCCAGTTACTTGCACTGGTACCAGCAGAGGTCAGGTGCCTCCCCCAAAATCTGGATTTATAGCACATCCAACTTGGCTTCTGGAGTCCCTGCTCGCTTCAGTGGCAGTGGGACTGGGACCTCTTACTCTCTCACAATCAGCAGTGTGGAGGCTGAAGATGCTGCCACTTATTACTGCCAGCAGTACAGTGGTTACCCGTGGACGTTCGGT GGAGGGACCAAGCTGGAGATC

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:919 as provided below.

[SEQ ID NO: 919] VQLQESGGGLVQPGGSRKLSCTASGFTFSSFGMHWVRQAPEKGLEWVAYISSGSNNIYFADTVKGRFTISRDNPKNTLFLQMTSLRSEDTAMYYCARSEY YGSSHMDYWGQGTTVTVSS

The nucleic acid sequence encoding the amino acid sequence of SEQ IDNO:3 is set forth in SEQ ID NO:920 as provided below.

[SEQ ID NO: 920] GTCCAACTGCAGGAGTCAGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCGGAAACTCTCCTGTACAGCCTCTGGATTCACTTTCAGTAGCTTTGGAATGCACTGGGTTCGTCAGGCTCCAGAGAAGGGGCTGGAGTGGGTCGCATACATTAGTAGTGGCAGTAATAACATCTACTTTGCGGACACAGTGAAGGGCCGATTCACCATCTCCAGAGACAATCCCAAGAACACCCTGTTCCTGCAAATGACCAGTCTAAGGTCTGAGGACACGGCCATGTATTACTGTGCAAGATCGGAATACTACGGTAGTAGCCATATGGACTACTGGGGCCAAGGGACCACGGTCACCGT CTCCTCA

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:921 as provided below.

[SEQ ID NO: 921] DIELTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYTSGG GTKLEI

The nucleic acid sequence encoding the amino acid sequence of SEQ IDNO:921 is set forth in SEQ ID NO:922 as provided below.

[SEQ ID NO: 922] GACATTGAGCTCACCCAGTCTCCAAAATTCATGTCCACATCAGTAGGAGACAGGGTCAGCGTCACCTGCAAGGCCAGTCAGAATGTGGGTACTAATGTAGCCTGGTATCAACAGAAACCAGGACAATCTCCTAAACCACTGATTTACTCGGCAACCTACCGGAACAGTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCACTAACGTGCAGTCTAAAGACTTGGCAGACTATTTCTGTCAACAATATAACAGGTATCCGTACACGTCCGGAGGG GGGACCAAGCTGGAGATC

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:144. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:144 is set forthin SEQ ID NO:142.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:143. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:143 is set forthin SEQ ID NO:141.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:216. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:216 is set forthin SEQ ID NO:214.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:215. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:215 is set forthin SEQ ID NO:213.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:220. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:220 is set forthin SEQ ID NO:218.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:219. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:219 is set forthin SEQ ID NO:217.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:236. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:236 is set forthin SEQ ID NO:234.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:235. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:235 is set forthin SEQ ID NO:232.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:268. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:268 is set forthin SEQ ID NO:266.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:267. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:267 is set forthin SEQ ID NO:265.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:172. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:172 is set forthin SEQ ID NO:170.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:171. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:171 is set forthin SEQ ID NO:169.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:116. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:116 is set forthin SEQ ID NO:114.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:115. The nucleic acidsequence encoding the amino acid sequence of SEQ ID NO:115 is set forthin SEQ ID NO:113.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising an aminoacid sequence selected from the group consisting of SEQ ID NO:3, SEQ IDNO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQ IDNO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ IDNO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ IDNO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ IDNO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ IDNO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143,SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ IDNO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199,SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ IDNO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255,SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ IDNO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917, SEQ ID NO:921and (b) a heavy chain variable region comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:4, SEQ ID NO:8, SEQ IDNO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQ ID NO:28, SEQ IDNO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ ID NO:48, SEQ IDNO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:68, SEQ IDNO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ IDNO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:108, SEQ IDNO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQ ID NO:128, SEQID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144, SEQ ID NO:148,SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:164, SEQ IDNO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQ ID NO:184, SEQID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200, SEQ ID NO:204,SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ ID NO:220, SEQ IDNO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQ ID NO:240, SEQID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256, SEQ ID NO:260,SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ ID NO:276, SEQ IDNO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQ ID NO:296, SEQID NO:300, SEQ ID NO:304, SEQ ID NO:917 and SEQ ID NO:921, wherein theextracellular binding domain binds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:3, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:4.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:7, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:8.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:11, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:12.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:15, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:16.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:19, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:20.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:23, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:24.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:27, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:28.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:31, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:32.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:35, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:36.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:39, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:40.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:43, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:44.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:47, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:48.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:51, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:52.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:55, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:56.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:59, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:60.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:63, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:64.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:67, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:68.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:71, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:72.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:75, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:76.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:79, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:80.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:83, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:84.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:87, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:88.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:91, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:92.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:95, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:96.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:99, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:100.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:103, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:104.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:107, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:108.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:111, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:112.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:115, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:116.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:119, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:120.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:123, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:124.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:127, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:128.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:131, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:132.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:135, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:136.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:139, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:140.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:143, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:144.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:147, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:148.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:151, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:152.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:155, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:156.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:159, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:160.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:163, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:164.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:167, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:168.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:171, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:172.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:175, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:176.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:179, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:180.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:183, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:184.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:187, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:188.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:191, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:192.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:195, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:196.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:199, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:200.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:203, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:204.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:207, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:208.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:211, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:212.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:215, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:216.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:219, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:220.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:223, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:224.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:227, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:228.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:231, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:232.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:235, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:236.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:239, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:240.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:243, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:244.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:247, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:248.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:251, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:252.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:255, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:256.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:259, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:260.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:263, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:264.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:267, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:268.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:271, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:272.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:275, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:276.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:279, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:280.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:283, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:284.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:287, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:288.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:291, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:292.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:279, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:280.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:283, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:284.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:287, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:288.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:291, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:292.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:295, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:296.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:299, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:300.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising amino acidshaving a sequence set forth in SEQ ID NO:303, and (b) a heavy chainvariable region comprising amino acids having a sequence set forth inSEQ ID NO:304.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:915, and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:917.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:919, and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:921.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises heavy and light chain variable regions comprising aminoacid sequences that are homologous to the amino acid sequences describedherein and as disclosed in Tables 1-76. For example, and not by way oflimitation, the extracellular antigen-binding domain (e.g., scFv)comprises a light chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:3,SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQID NO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ IDNO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ IDNO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ IDNO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ IDNO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143,SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ IDNO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199,SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ IDNO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255,SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ IDNO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917 and SEQ IDNO:921.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:4,SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQID NO:28, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ IDNO:48, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ IDNO:68, SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ IDNO:88, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ IDNO:108, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQID NO:128, SEQ ID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144,SEQ ID NO:148, SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ IDNO:164, SEQ ID NO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQID NO:184, SEQ ID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200,SEQ ID NO:204, SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ IDNO:220, SEQ ID NO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQID NO:240, SEQ ID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256,SEQ ID NO:260, SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ IDNO:276, SEQ ID NO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQID NO:296, SEQ ID NO:300, SEQ ID NO:304, SEQ ID NO:915 and SEQ IDNO:919.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising an aminoacid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologousto an amino acid sequence selected from the group consisting of SEQ IDNO:3, SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ IDNO:23, SEQ ID NO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ IDNO:43, SEQ ID NO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ IDNO:63, SEQ ID NO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ IDNO:83, SEQ ID NO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ IDNO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQID NO:123, SEQ ID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139,SEQ ID NO:143, SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ IDNO:159, SEQ ID NO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQID NO:179, SEQ ID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195,SEQ ID NO:199, SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ IDNO:215, SEQ ID NO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQID NO:235, SEQ ID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251,SEQ ID NO:255, SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ IDNO:271, SEQ ID NO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQID NO:291, SEQ ID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917and SEQ ID NO:921; and (b) a heavy chain variable region comprising anamino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%,87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%homologous to an amino acid sequence selected from the group consistingof SEQ ID NO:4, SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20,SEQ ID NO:24, SEQ ID NO:28, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40,SEQ ID NO:44, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60,SEQ ID NO:64, SEQ ID NO:68, SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80,SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100,SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:116, SEQ IDNO:120, SEQ ID NO:124, SEQ ID NO:128, SEQ ID NO:132, SEQ ID NO:136, SEQID NO:140, SEQ ID NO:144, SEQ ID NO:148, SEQ ID NO:152, SEQ ID NO:156,SEQ ID NO:160, SEQ ID NO:164, SEQ ID NO:168, SEQ ID NO:172, SEQ IDNO:176, SEQ ID NO:180, SEQ ID NO:184, SEQ ID NO:188, SEQ ID NO:192, SEQID NO:196, SEQ ID NO:200, SEQ ID NO:204, SEQ ID NO:208, SEQ ID NO:212,SEQ ID NO:216, SEQ ID NO:220, SEQ ID NO:224, SEQ ID NO:228, SEQ IDNO:232, SEQ ID NO:236, SEQ ID NO:240, SEQ ID NO:244, SEQ ID NO:248, SEQID NO:252, SEQ ID NO:256, SEQ ID NO:260, SEQ ID NO:264, SEQ ID NO:268,SEQ ID NO:272, SEQ ID NO:276, SEQ ID NO:280, SEQ ID NO:284, SEQ IDNO:288, SEQ ID NO:292, SEQ ID NO:296, SEQ ID NO:300, SEQ ID NO:304, SEQID NO:915 and SEQ ID NO:919.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising an aminoacid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologousto the amino acid sequence set forth in SEQ ID NO:143, and (b) a heavychain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:144, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising an aminoacid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologousto the amino acid sequence set forth in SEQ ID NO:215, and (b) a heavychain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:216, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising an aminoacid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologousto the amino acid sequence set forth in SEQ ID NO:219, and (b) a heavychain variable comprising an amino acid sequence that is at least 80%,81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:220, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous tothe amino acid sequence set forth in SEQ ID NO:235, and (b) a heavychain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:236, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region comprising an aminoacid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologousto the amino acid sequence set forth in SEQ ID NO:267, and (b) a heavychain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:268, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region comprising an aminoacid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologousto the amino acid sequence set forth in SEQ ID NO:915, and (b) a lightchain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:917, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region comprising an aminoacid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologousto the amino acid sequence set forth in SEQ ID NO:919, and (b) a lightchain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:921, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous tothe amino acid sequence set forth in SEQ ID NO:115, and (b) a heavychain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:116, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous tothe amino acid sequence set forth in SEQ ID NO:171, and (b) a heavychain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to the amino acid sequence setforth in SEQ ID NO:172, wherein the extracellular antigen-binding domainbinds to an FcRL5 polypeptide.

An extracellular antigen-binding domain (e.g., scFv) comprising V_(H)and/or V_(L) regions having high (i.e., 80% or greater) homology to theV_(H) and V_(L) regions of the sequences set forth above, can beobtained by mutagenesis (e.g., site-directed or PCR-mediatedmutagenesis), followed by testing of the encoded altered scFv forretained function (i.e., the binding affinity) using the binding assaysdescribed herein. In certain embodiments, a V_(L) sequence having atleast 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identitycontains substitutions (e.g., conservative substitutions to generateconservative modifications of a sequence), insertions or deletionsrelative to the reference sequence, but an extracellular antigen-bindingdomain (e.g., scFv) comprising that sequence retains the ability to bindto FcRL5. In certain embodiments, a V_(H) sequence having at least 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity containssubstitutions (e.g., conservative substitutions), insertions ordeletions relative to the reference sequence, but an extracellularantigen-binding domain (e.g., scFv) comprising that sequence retains theability to bind to FcRL5. In certain embodiments, a total of about 1 toabout 10 amino acids have been substituted, inserted and/or deleted inthe disclosed sequences. For example, and not by way of limitation, aV_(H) sequence or a V_(L) sequence, can have up to about one, up toabout two, up to about three, up to about four, up to about five, up toabout six, up to about seven, up to about eight, up to about nine or upto about ten amino acid residues that are modified and/or substituted.Non-limiting examples of conservative modifications are provided below,e.g., within Table 231.

The presently disclosed subject matter further provides extracellularantigen-binding domains (e.g., scFv) that comprise heavy chain variableregion and light chain variable region CDRs, e.g., CDR1s, CDR2s andCDR3s, as disclosed herein in Tables 229 and 230. The CDR regions aredelineated using the Kabat system (Kabat, E. A., et al. (1991) Sequencesof Proteins of Immunological Interest, Fifth Edition, U.S. Department ofHealth and Human Services, NIH Publication No. 91-3242). The presentdisclosure further provides extracellular antigen-binding domains (e.g.,scFv) that comprise conservative modifications of the antibody sequencesdisclosed herein. For example, and not by way of limitation, anextracellular antigen-binding domains (e.g., scFv) of the presentlydisclosed subject matter comprises a heavy chain variable regioncomprising CDR1, CDR2 and CDR3 sequences and a light chain variableregion comprising CDR1, CDR2 and CDR3 sequences, wherein one or more ofthese CDR sequences comprise specified amino acid sequences disclosedherein, or conservative modifications thereof, and wherein theextracellular antigen-binding domains retain the desired functionalproperties. See Tables 229 and 230.

In certain embodiments, the presently disclosed subject matter providesan extracellular antigen-binding domain (e.g., scFv) comprising a lightchain variable region, wherein the light chain variable regioncomprises: (a) a CDR1 comprising an amino acid sequence selected fromthe group consisting of SEQ ID NOs: 312, 3118, 324, 329, 338, 343, 348,352, 357, 363, 369, 381, 390, 397, 401, 406, 416, 423, 428, 433, 447,460, 468, 474, 477, 483, 490, 498, 503, 508, 518, 533, 540, 544, 547,556, 562, 568, 571, 580, 585, 588, 926 and 932, and conservativemodifications thereof (b) a CDR2 comprising an amino acid sequenceselected from the group consisting of SEQ ID NOs:313, 319, 330, 344,349, 358, 364, 370, 382, 385, 391, 398, 409, 417, 429, 434, 438, 448,454, 461, 469, 478, 484, 487, 504, 513, 523, 534, 429, 448, 548, 557,563, 572, 575, 586, 927 and 933, and conservative modifications thereof;and (c) a CDR3 comprising an amino acid sequence selected from the groupconsisting of SEQ ID NOs: 314, 320, 325, 331, 339, 345, 350, 353, 359,365, 371, 377, 383, 386, 392, 395, 399, 402, 407, 410, 414, 418, 419,424, 430, 435, 439, 443, 449, 452, 455, 457, 462, 465, 470, 479, 485,488, 491, 493, 495, 499, 505, 509, 514, 519, 524, 528, 530, 531, 535,541, 542, 545, 549, 554, 558, 564, 569, 573, 576, 581, 592, 928 and 934,and conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region, wherein the heavy chainvariable region comprises: (a) a CDR1 comprising an amino acid sequenceselected from the group consisting of SEQ ID NOs: 309, 315, 321, 326,332, 335, 340, 346, 354, 360, 366, 372, 378, 387, 393, 403, 411, 420,425, 436, 440, 444, 471, 480, 500, 510, 515, 520, 525, 537, 551, 559,565, 582, 589, 923 and 929 and conservative modifications thereof (b) aCDR2 comprising an amino acid sequence selected from the groupconsisting of SEQ ID NOs: 310, 316, 322, 327, 333, 336, 341, 355, 361,367, 373, 379, 388, 404, 412, 421, 426, 431, 441, 445, 450, 466, 472,475, 481, 496, 501, 506, 511, 516, 521, 526, 538, 552, 560, 566, 583,590, 924 and 930 and conservative modifications thereof; and (c) a CDR3comprising an amino acid sequence selected from the group consisting ofSEQ ID NOs: 311, 317, 323, 328, 334, 337, 342, 347, 351, 356, 362, 368,374, 376, 380, 384, 389, 394, 396, 400, 405, 408, 412, 415, 422, 427,432, 437, 442, 446, 451, 453, 456, 458, 459, 463, 464, 467, 473, 476,482, 486, 489, 492, 494, 497, 502, 507, 512, 517, 522, 527, 529, 532,536, 539, 543, 546, 550, 553, 555, 561, 567, 570, 574, 577, 578, 579,584, 578, 587, 591, 925 and 931, and conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:411 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:412 or conservative modifications thereof and(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:463 or conservative modifications thereof. Incertain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:318 or conservative modificationsthereof; (b) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:319 or conservative modifications thereof;and (c) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:419 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:515 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:516 or conservative modifications thereof;and (c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:517 or conservative modifications thereof. Incertain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:318 or conservative modificationsthereof; (b) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:319 or conservative modifications thereof;and (c) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:531 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:403 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:404 or conservative modifications thereof and(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:532 or conservative modifications thereof. Incertain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:533 or conservative modificationsthereof; (b) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:534 or conservative modifications thereof;and (c) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:535 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:411 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:412 or conservative modifications thereof;and (c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:543 or conservative modifications thereof. Incertain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:544 or conservative modificationsthereof (b) a light chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:448 or conservative modifications thereof; and (c)a light chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:545 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:372 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:475 or conservative modifications thereof and(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:570 or conservative modifications thereof. Incertain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:571 or conservative modificationsthereof; (b) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:572 or conservative modifications thereof;and (c) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:573 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:440 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:441 or conservative modifications thereof;and (c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:442 or conservative modifications thereof. Incertain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:329 or conservative modificationsthereof; (b) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:330 or conservative modifications thereof;and (c) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:443 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:309 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:310 or conservative modifications thereof;and (c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:489 or conservative modifications thereof. Incertain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a light chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:490 or conservative modificationsthereof; (b) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:313 or conservative modifications thereof;and (c) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:491 or conservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising aminoacids having the sequence set forth in SEQ ID NO:923 or conservativemodifications thereof; (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:924 orconservative modifications thereof; and (c) a heavy chain variableregion CDR3 comprising amino acids having the sequence set forth in SEQID NO:925 or conservative modifications thereof. In certain embodiments,the extracellular antigen-binding domain comprises (a) a light chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:926 or conservative modifications thereof; (b) alight chain variable region CDR2 comprising amino acids having thesequence set forth in SEQ ID NO:927 or conservative modificationsthereof; and (c) a light chain variable region CDR3 comprising aminoacids having the sequence set forth in SEQ ID NO:928 or conservativemodifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising aminoacids having the sequence set forth in SEQ ID NO:929 or conservativemodifications thereof; (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:930 orconservative modifications thereof; and (c) a heavy chain variableregion CDR3 comprising amino acids having the sequence set forth in SEQID NO:931 or conservative modifications thereof. In certain embodiments,the extracellular antigen-binding domain comprises (a) a light chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:932 or conservative modifications thereof; (b) alight chain variable region CDR2 comprising amino acids having thesequence set forth in SEQ ID NO: 933 or conservative modificationsthereof; and (c) a light chain variable region CDR3 comprising aminoacids having the sequence set forth in SEQ ID NO:934 or conservativemodifications thereof.

The presently disclosed subject matter provides an extracellularantigen-binding domain (e.g., scFv) comprising a heavy chain variableregion comprising CDR1, CDR2, and CDR3 sequences and a light chainvariable region comprising CDR1, CDR2, and CDR3 sequences, wherein: (a)the heavy chain variable region CDR3 comprises an amino acid sequenceselected from the group consisting of SEQ ID NOs: 311, 317, 323, 328,334, 337, 342, 347, 351, 356, 362, 368, 374, 376, 380, 384, 389, 394,396, 400, 405, 408, 412, 415, 422, 427, 432, 437, 442, 446, 451, 453,456, 458, 459, 463, 464, 467, 473, 476, 482, 486, 489, 492, 494, 497,502, 507, 512, 517, 522, 527, 529, 532, 536, 539, 543, 546, 550, 553,555, 561, 567, 570, 574, 577, 578, 579, 584, 578, 587, 591, 925 and 931,and conservative modifications thereof; and (b) the light chain variableregion CDR3 comprises an amino acid sequence selected from the groupconsisting of SEQ ID NOs: 314, 320, 325, 331, 339, 345, 350, 353, 359,365, 371, 377, 383, 386, 392, 395, 399, 402, 407, 410, 414, 418, 419,424, 430, 435, 439, 443, 449, 452, 455, 457, 462, 465, 470, 479, 485,488, 491, 493, 495, 499, 505, 509, 514, 519, 524, 528, 530, 531, 535,541, 542, 545, 549, 554, 558, 564, 569, 573, 576, 581, 592, 928 and 934and conservative modifications thereof; wherein the extracellularantigen-binding domain specifically binds to human FcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising theamino acid sequence of SEQ ID NO:463 or conservative modificationsthereof; and (b) a light chain variable region CDR3 comprising the aminoacid sequence of SEQ ID NO:419 or conservative modifications thereof;wherein the extracellular antigen-binding domain specifically bindsFcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising theamino acid sequence of SEQ ID NO:517 or conservative modificationsthereof; and (b) a light chain variable region CDR3 comprising the aminoacid sequence of SEQ ID NO:531 or conservative modifications thereof;wherein the extracellular antigen-binding domain specifically bindsFcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising theamino acid sequence of SEQ ID NO:532 or conservative modificationsthereof; and (b) a light chain variable region CDR3 comprising the aminoacid sequence of SEQ ID NO:535 or conservative modifications thereof;wherein the antibody or antigen-binding fragment thereof specificallybinds FcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising theamino acid sequence of SEQ ID NO:543 or conservative modificationsthereof; and (b) a light chain variable region CDR3 comprising the aminoacid sequence of SEQ ID NO:545 or conservative modifications thereof;wherein the extracellular antigen-binding domain specifically bindsFcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising theamino acid sequence of SEQ ID NO:570 or conservative modificationsthereof; and (b) a light chain variable region CDR3 comprising the aminoacid sequence of SEQ ID NO:573 or conservative modifications thereof;wherein the antibody or antigen-binding fragment thereof specificallybinds FcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising aminoacids having the sequence set forth in SEQ ID NO:925 or conservativemodifications thereof; and (b) and a light chain variable region CDR3comprising amino acids having the sequence set forth in SEQ ID NO:928 orconservative modifications thereof; wherein the extracellularantigen-binding domain specifically binds FcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising aminoacids having the sequence set forth in SEQ ID NO:931 or conservativemodifications thereof; and (b) a light chain variable region CDR3comprising amino acids having the sequence set forth in SEQ ID NO:934 orconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising theamino acid sequence of SEQ ID NO:442 or conservative modificationsthereof; and (b) a light chain variable region CDR3 comprising the aminoacid sequence of SEQ ID NO:443 or conservative modifications thereofwherein the extracellular antigen-binding domain specifically bindsFcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR3 comprising theamino acid sequence of SEQ ID NO:489 or conservative modificationsthereof; and (b) a light chain variable region CDR3 comprising the aminoacid sequence of SEQ ID NO:491 or conservative modifications thereofwherein the extracellular antigen-binding domain specifically bindsFcRL5.

In certain embodiments, the presently disclosed subject matter providesan extracellular antigen-binding domain (e.g., scFv) comprising a heavychain variable region comprising CDR1, CDR2, and CDR3 sequences and alight chain variable region comprising CDR1, CDR2, and CDR3 sequences,wherein: (a) the heavy chain variable region CDR1 comprises an aminoacid sequence selected from the group consisting of SEQ ID NOs: 309,315, 321, 326, 332, 335, 340, 346, 354, 360, 366, 372, 378, 387, 393,403, 411, 420, 425, 436, 440, 444, 471, 480, 500, 510, 515, 520, 525,537, 551, 559, 565, 582, 589, 923 and 929, and conservativemodifications thereof; (b) the heavy chain variable region CDR2comprises an amino acid sequence selected from the group consisting ofSEQ ID NOs: 310, 316, 322, 327, 333, 336, 341, 355, 361, 367, 373, 379,388, 404, 412, 421, 426, 431, 441, 445, 450, 466, 472, 475, 481, 496,501, 506, 511, 516, 521, 526, 538, 552, 560, 566, 583, 590, 924 and 930,and conservative modifications thereof; (c) the heavy chain variableregion CDR3 comprises an amino acid sequence selected from the groupconsisting of SEQ ID NOs: 311, 317, 323, 328, 334, 337, 342, 347, 351,356, 362, 368, 374, 376, 380, 384, 389, 394, 396, 400, 405, 408, 412,415, 422, 427, 432, 437, 442, 446, 451, 453, 456, 458, 459, 463, 464,467, 473, 476, 482, 486, 489, 492, 494, 497, 502, 507, 512, 517, 522,527, 529, 532, 536, 539, 543, 546, 550, 553, 555, 561, 567, 570, 574,577, 578, 579, 584, 578, 587, 591, 925 and 931 and conservativemodifications thereof; (d) the light chain variable region CDR1comprises an amino acid sequence selected from the group consisting ofSEQ ID NOs: 312, 3118, 324, 329, 338, 343, 348, 352, 357, 363, 369, 381,390, 397, 401, 406, 416, 423, 428, 433, 447, 460, 468, 474, 477, 483,490, 498, 503, 508, 518, 533, 540, 544, 547, 556, 562, 568, 571, 580,585, 588, 926 and 932 and conservative modifications thereof; (e) thelight chain variable region CDR2 comprises an amino acid sequenceselected from the group consisting of SEQ ID NOs:313, 319, 330, 344,349, 358, 364, 370, 382, 385, 391, 398, 409, 417, 429, 434, 438, 448,454, 461, 469, 478, 484, 487, 504, 513, 523, 534, 429, 448, 548, 557,563, 572, 575, 586, 927 and 933 and conservative modifications thereof;and (f) the light chain variable region CDR3 comprises an amino acidsequence selected from the group consisting of SEQ ID NOs: 314, 320,325, 331, 339, 345, 350, 353, 359, 365, 371, 377, 383, 386, 392, 395,399, 402, 407, 410, 414, 418, 419, 424, 430, 435, 439, 443, 449, 452,455, 457, 462, 465, 470, 479, 485, 488, 491, 493, 495, 499, 505, 509,514, 519, 524, 528, 530, 531, 535, 541, 542, 545, 549, 554, 558, 564,569, 573, 576, 581, 592, 928 and 934 and conservative modificationsthereof; wherein the extracellular antigen-binding domain specificallybinds FcRL5.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:411 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:412 or conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:463 or conservative modifications thereof; (d) alight chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:318 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:319or conservative modifications thereof; and (f) a light chain variableregion CDR3 comprising the amino acid sequence of SEQ ID NO:419 orconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:515 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:516 or conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:517 or conservative modifications thereof; (d) alight chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:318 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:319or conservative modifications thereof; and (f) a light chain variableregion CDR3 comprising the amino acid sequence of SEQ ID NO:531 orconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:403 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:404 or conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:532 or conservative modifications thereof; (d) alight chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:533 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:534or conservative modifications thereof; and (f) a light chain variableregion CDR3 comprising the amino acid sequence of SEQ ID NO:535 orconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:411 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:412 or conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:543 or conservative modifications thereof; (d) alight chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:544 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:448or conservative modifications thereof; and (f) a light chain variableregion CDR3 comprising the amino acid sequence of SEQ ID NO:545 orconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:372 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:475 or conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:570 or conservative modifications thereof; (d) alight chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:571 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:572or conservative modifications thereof; and (f) a light chain variableregion CDR3 comprising the amino acid sequence of SEQ ID NO:573 orconservative modifications thereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising aminoacids having the sequence set forth in SEQ ID NO:923 or conservativemodifications thereof; (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:924 orconservative modifications thereof; (c) a heavy chain variable regionCDR3 comprising amino acids having the sequence set forth in SEQ IDNO:925 or conservative modifications thereof; (d) a light chain variableregion CDR1 comprising amino acids having the sequence set forth in SEQID NO:926 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising amino acids having the sequence setforth in SEQ ID NO:927 or conservative modifications thereof; and (f)and a light chain variable region CDR3 comprising amino acids having thesequence set forth in SEQ ID NO:928 or conservative modificationsthereof.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises (a) a heavy chain variable region CDR1 comprising aminoacids having the sequence set forth in SEQ ID NO:929 or conservativemodifications thereof; (b) a heavy chain variable region CDR2 comprisingamino acids having the sequence set forth in SEQ ID NO:930 orconservative modifications thereof; (c) a heavy chain variable regionCDR3 comprising amino acids having the sequence set forth in SEQ IDNO:931 or conservative modifications thereof (d) a light chain variableregion CDR1 comprising amino acids having the sequence set forth in SEQID NO:932 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising amino acids having the sequence setforth in SEQ ID NO:933 or conservative modifications thereof, and (f) alight chain variable region CDR3 comprising amino acids having thesequence set forth in SEQ ID NO:934 or conservative modificationsthereof.

In certain embodiments, a presently disclosed anti-FcRL5 antibody orantigen-binding fragment thereof comprises: (a) a heavy chain variableregion CDR1 comprising the amino acid sequence of SEQ ID NO:440 orconservative modifications thereof; (b) a heavy chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:441 or conservativemodifications thereof (c) a heavy chain variable region CDR3 comprisingthe amino acid sequence of SEQ ID NO:442 or conservative modificationsthereof (d) a light chain variable region CDR1 comprising the amino acidsequence of SEQ ID NO:329 or conservative modifications thereof; (e) alight chain variable region CDR2 comprising the amino acid sequence ofSEQ ID NO:330 or conservative modifications thereof; and (f) a lightchain variable region CDR3 comprising the amino acid sequence of SEQ IDNO:443 or conservative modifications thereof.

In certain embodiments, a presently disclosed anti-FcRL5 antibody orantigen-binding fragment thereof comprises: (a) a heavy chain variableregion CDR1 comprising the amino acid sequence of SEQ ID NO:309 orconservative modifications thereof; (b) a heavy chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:310 or conservativemodifications thereof; (c) a heavy chain variable region CDR3 comprisingthe amino acid sequence of SEQ ID NO:489 or conservative modificationsthereof; (d) a light chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:490 or conservative modifications thereof;(e) a light chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:313 or conservative modifications thereof; and (f)a light chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:491 or conservative modifications thereof.

As used herein, the terms “conservative sequence modifications” and“conservative modifications” refers to amino acid modifications that donot significantly affect or alter the binding characteristics of thepresently disclosed CAR (e.g., the extracellular antigen-binding domain)comprising the amino acid sequence. Such conservative modificationsinclude amino acid substitutions, additions and deletions. Modificationscan be introduced into the human scFv of the presently disclosed subjectmatter by standard techniques known in the art, such as site-directedmutagenesis and PCR-mediated mutagenesis. Amino acids can be classifiedinto groups according to their physicochemical properties such as chargeand polarity.

Conservative amino acid substitutions are ones in which the amino acidresidue is replaced with an amino acid within the same group. Forexample, amino acids can be classified by charge: positively-chargedamino acids include lysine, arginine, histidine, negatively-chargedamino acids include aspartic acid, glutamic acid, neutral charge aminoacids include alanine, asparagine, cysteine, glutamine, glycine,isoleucine, leucine, methionine, phenylalanine, proline, serine,threonine, tryptophan, tyrosine, and valine. In addition, amino acidscan be classified by polarity: polar amino acids include arginine (basicpolar), asparagine, aspartic acid (acidic polar), glutamic acid (acidicpolar), glutamine, histidine (basic polar), lysine (basic polar),serine, threonine, and tyrosine; non-polar amino acids include alanine,cysteine, glycine, isoleucine, leucine, methionine, phenylalanine,proline, tryptophan, and valine. Thus, one or more amino acid residueswithin a CDR region can be replaced with other amino acid residues fromthe same group and the altered antibody can be tested for retainedfunction (i.e., the functions set forth in (c) through (l) above) usingthe functional assays described herein. In certain embodiments, no morethan one, no more than two, no more than three, no more than four, nomore than five residues within a specified sequence or a CDR region arealtered. Exemplary conservative amino acid substitutions are shown inTable 231.

TABLE 231 Original Exemplary conservative Residue amino acidSubstitutions Ala (A) Val; Leu; Ile Arg (R) Lys; Gln; Asn Asn (N) Gln;His; Asp, Lys; Arg Asp (D) Glu; Asn Cys (C) Ser; Ala Gln (Q) Asn; GluGlu (E) Asp; Gln Gly (G) Ala His (H) Asn; Gln; Lys; Arg Ile (I) Leu;Val; Met; Ala; Phe Leu (L) Ile; Val; Met; Ala; Phe Lys (K) Arg; Gln; AsnMet (M) Leu; Phe; Ile Phe (F) Trp; Leu; Val; Ile; Ala; Tyr Pro (P) AlaSer (S) Thr Thr (T) Val; Ser Trp (W) Tyr; Phe Tyr (Y) Trp; Phe; Thr; SerVal (V) Ile; Leu; Met; Phe; Ala

In certain non-limiting embodiments, an extracellular antigen-bindingdomain of the CAR can comprise a linker connecting the heavy chainvariable region and light chain variable region of the extracellularantigen-binding domain. As used herein, the term “linker” refers to afunctional group (e.g., chemical or polypeptide) that covalentlyattaches two or more polypeptides or nucleic acids so that they areconnected to one another. As used herein, a “peptide linker” refers toone or more amino acids used to couple two proteins together (e.g., tocouple V_(H) and V_(L) domains). Non-limiting examples of peptidelinkers are disclosed in Shen et al., Anal. Chem. 80(6):1910-1917(2008).

In one non-limiting example, the linker is a G4S linker that comprisesamino acids having the sequence set forth in SEQ ID NO:897. In certainembodiments, the nucleotide sequence encoding the amino acid sequence ofSEQ ID NO:897 is set forth in SEQ ID NO:898. In one non-limitingexample, the linker comprises amino acids having the sequence set forthin SEQ ID NO:307. In certain embodiments, the nucleotide sequenceencoding the amino acid sequence of SEQ ID NO:307 is set forth in SEQ IDNO:305.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:901 as provided below.

[SEQ ID NO: 901] GGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:902 as provided below.

[SEQ ID NO: 902] SGGSGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:903 as provided below.

[SEQ ID NO: 903] GGGGSGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:904 as provided below.

[SEQ ID NO: 904] GGGGSGGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:905 as provided below.

[SEQ ID NO: 905] GGGGSGGGGSGGGGGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:906 as provided below.

[SEQ ID NO: 906] GGGGSGGGGSGGGGSGGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:907 as provided below.

[SEQ ID NO: 907] GGGGSGGGGSGGGGSGGGGSGGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:908 as provided below.

[SEQ ID NO: 908] GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:909 as provided below.

[SEQ ID NO: 909] GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:910 as provided below.

[SEQ ID NO: 910] EPKSCDKTHTCPPCP.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:911 as provided below.

[SEQ ID NO: 911] GGGGSGGGSEPKSCDKTHTCPPCP.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:912 as provided below.

[SEQ ID NO: 912] ELKTPLGDTTHTCPRCPEPKSCDTPPPCPRCPEPKSCDTPPPCPRCPEPKSCDTPPPCPRCP.

In certain embodiments, the linker comprises amino acids having thesequence set forth in SEQ ID NO:913 as provided below.

[SEQ ID NO: 913] GSGSGS.

In certain embodiments, the the linker comprises amino acids having thesequence set forth in SEQ ID NO:914 as provided below.

[SEQ ID NO: 914] AAA.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) comprises a heavy chain variable region, a light chain variableregion and a linker peptide between the heavy chain variable region andthe light chain variable region. Non-limiting examples of extracellularantigen-binding domains, e.g., scFvs, of the present disclosure thatcomprise a heavy chain variable region, a light chain variable regionand a linker peptide are disclosed in Tables 77-152. For example, andnot by way of limitation, the extracellular antigen-binding domaincomprising a heavy chain variable region, a light chain variable regionand a linker peptide of the present disclosure comprises an amino acidsequence selected from the group consisting of SEQ ID NO:594, SEQ IDNO:596, SEQ ID NO:598, SEQ ID NO:600, SEQ ID NO:602, SEQ ID NO:604, SEQID NO:606, SEQ ID NO:608, SEQ ID NO:610, SEQ ID NO:612, SEQ ID NO:614,SEQ ID NO:616, SEQ ID NO:618, SEQ ID NO:620, SEQ ID NO:622, SEQ IDNO:624, SEQ ID NO:626, SEQ ID NO:628, SEQ ID NO:630, SEQ ID NO:632, SEQID NO:634, SEQ ID NO:636, SEQ ID NO:638, SEQ ID NO:640, SEQ ID NO:642,SEQ ID NO:644, SEQ ID NO:646, SEQ ID NO:648, SEQ ID NO:650, SEQ IDNO:652, SEQ ID NO:654, SEQ ID NO:656, SEQ ID NO:658, SEQ ID NO:660, SEQID NO:662, SEQ ID NO:664, SEQ ID NO:666, SEQ ID NO:668, SEQ ID NO:670,SEQ ID NO:672, SEQ ID NO:674, SEQ ID NO:676, SEQ ID NO:678, SEQ IDNO:680, SEQ ID NO:682, SEQ ID NO:684, SEQ ID NO:686, SEQ ID NO:688, SEQID NO:690, SEQ ID NO:692, SEQ ID NO:694, SEQ ID NO:696, SEQ ID NO:698,SEQ ID NO:700, SEQ ID NO:702, SEQ ID NO:704, SEQ ID NO:706, SEQ IDNO:708, SEQ ID NO:710, SEQ ID NO:712, SEQ ID NO:714, SEQ ID NO:716, SEQID NO:718, SEQ ID NO:720, SEQ ID NO:722, SEQ ID NO:724, SEQ ID NO:726,SEQ ID NO:728, SEQ ID NO:730, SEQ ID NO:732, SEQ ID NO:734, SEQ IDNO:736, SEQ ID NO:738, SEQ ID NO:740, SEQ ID NO:742, SEQ ID NO:744 andconservative modifications of (as shown in Tables 77-152).

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:650 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:664 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:678 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:700 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:702 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:710 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:726 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:650 or conservative modifications of.

In certain embodiments, the extracellular antigen-binding domain (e.g.,scFv) having a heavy chain variable region, a light chain variableregion and a linker peptide comprises the amino acid sequence of SEQ IDNO:678 or conservative modifications of.

In addition, the extracellular antigen-binding domain can comprise aleader or a signal peptide that directs the nascent protein into theendoplasmic reticulum. Signal peptide or leader can be essential if theCAR is to be glycosylated and anchored in the cell membrane. The signalsequence or leader can be a peptide sequence (about 5, about 10, about15, about 20, about 25, or about 30 amino acids long) present at theN-terminus of newly synthesized proteins that directs their entry to thesecretory pathway. In non-limiting examples, the signal peptide iscovalently joined to the 5′ terminus of the extracellularantigen-binding domain. In certain embodiments, the signal peptidecomprises a CD8 polypeptide comprising amino acids having the sequenceset forth in SEQ ID NO:26 as provided below.

[SEQ ID NO: 935] MALPVTALLLPLALLLHAARThe nucleotide sequence encoding the amino acid sequence of SEQ IDNO:935 is set forth in SEQ ID NO:936, which is provided below:

[SEQ ID NO: 936] ATGGCTCTCCCAGTGACTGCCCTACTGCTTCCCCTAGCGCTTCTCCTGCATGCAGCTCGT

In another embodiment, the signal peptide comprises amino acids havingthe sequence set forth in SEQ ID NO:937 as provided below.

[SEQ ID NO: 937] METDTLLLWVLLLWVPGSTGThe nucleotide sequence encoding the amino acid sequence of SEQ IDNO:937 is set forth in SEQ ID NO:938, which is provided below:

[SEQ ID NO: 938] ATGGAAACCGACACCCTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGA

In certain embodiments, the extracellular antigen-binding domain, e.g.,the human scFv, comprises a heavy chain variable region, a light chainvariable region, a linker peptide between the heavy chain variableregion and the light chain variable region, and an His-tag and anHA-tag. In certain embodiments, the amino acid sequence of the His-tagand HA-tag comprises the amino acid sequence of SEQ ID NO:308. Thenucleotide sequence encoding SEQ ID NO: 308 is SEQ ID NO: 306.

In certain embodiments, the extracellular antigen-binding domain, e.g.,the human scFv, binds to a human FcRL5 polypeptide comprising the aminoacid sequence set forth in SEQ ID NO: 899. In certain embodiments, theextracellular antigen-binding domain, e.g., the human scFv, binds to anepitope in domain 9 (e.g., amino acids 754-835 of SEQ ID NO:899). Incertain embodiments, the extracellular antigen-binding domain, e.g., thehuman scFv, binds to an epitope in domain 8 (e.g., amino acids 658-731of SEQ ID NO:899). In certain embodiments, the extracellularantigen-binding domain, e.g., the human scFv, binds to an epitope withindomain 9 comprising amino acids 829-840 of SEQ ID NO:899. In certainembodiments, the extracellular antigen-binding domain, e.g., the humanscFv, binds to an epitope within domain 8 comprising amino acids 657-667of SEQ ID NO:899. For example, and not by way of limitation, theextracellular antigen-binding domain, e.g., the human scFv, binds to anepitope comprising the amino acid sequence RSETVTLYITGL (SEQ ID NO:964).In certain embodiments, In certain embodiments, an antibody or anantigen-binding fragment thereof of the present disclosure binds to anepitope comprising the amino acid sequence SRPILTFRAPR (SEQ ID NO:965).

Transmembrane Domain of a CAR

In certain non-limiting embodiments, the transmembrane domain of the CARcomprises a hydrophobic alpha helix that spans at least a portion of themembrane. Different transmembrane domains result in different receptorstability. After antigen recognition, receptors cluster and a signal istransmitted to the cell. In accordance with the presently disclosedsubject matter, the transmembrane domain of the CAR can comprise a CD8polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD4 polypeptide,a 4-1BB polypeptide, an OX40 polypeptide, an ICOS polypeptide, a CTLA-4polypeptide, a PD-1 polypeptide, a LAG-3 polypeptide, a 2B4 polypeptide,a BTLA polypeptide, a synthetic peptide (not based on a proteinassociated with the immune response), or a combination thereof.

In certain embodiments, the transmembrane domain of a presentlydisclosed CAR comprises a CD28 polypeptide. The CD28 polypeptide canhave an amino acid sequence that is at least about 85%, about 90%, about95%, about 96%, about 97%, about 98%, about 99% or 100% homologous tothe sequence having a NCBI Reference No: P10747 or NP_006130 (SEQ IDNO:939), or fragments thereof, and/or may optionally comprise up to oneor up to two or up to three conservative amino acid substitutions. Innon-limiting embodiments, the CD28 polypeptide can have an amino acidsequence that is a consecutive portion of SEQ ID NO:939 which is atleast 20, or at least 30, or at least 40, or at least 50, and up to 220amino acids in length. Alternatively or additionally, in non-limitingvarious embodiments, the CD28 polypeptide has an amino acid sequence ofamino acids 1 to 220, 1 to 50, 50 to 100, 100 to 150, 150 to 200, or 200to 220 of SEQ ID NO:939. In certain embodiments, the CAR of thepresently disclosed subject matter comprises a transmembrane domaincomprising a CD28 polypeptide, and an intracellular domain comprising aco-stimulatory signaling region that comprises a CD28 polypeptide. Incertain embodiments, the CD28 polypeptide comprised in the transmembranedomain and the intracellular domain has an amino acid sequence of aminoacids 114 to 220 of SEQ ID NO:939.

SEQ ID NO:939 is provided below:

[SEQ ID NO: 939] 1 MLRLLLALNL FPSIQVTGNK ILVKQSPMLV AYDNAVNLSCKYSYNLFSRE FRASLHKGLD 61 SAVEVCVVYG NYSQQLQVYS KTGFNCDGKL GNESVTFYLQNLYVNQTDIY FCKIEVMYPP 121 PYLDNEKSNG TIIHVKGKHL CPSPLFPGPS KPFWVLVVVGGVLACYSLLV TVAFIIFWVR 181 SKRSRLLHSD YMNMTPRRPG PTRKHYQPYA PPRDFAAYRS

In accordance with the presently disclosed subject matter, a “CD28nucleic acid molecule” refers to a polynucleotide encoding a CD28polypeptide. In certain embodiments, the CD28 nucleic acid moleculeencoding the CD28 polypeptide comprised in the transmembrane domain andthe intracellular domain (e.g., the co-stimulatory signaling region) ofthe presently disclosed CAR (amino acids 114 to 220 of SEQ ID NO:939)comprises nucleic acids having the sequence set forth in SEQ ID NO:940as provided below.

[SEQ ID NO: 940] ATTGAAGTTATGTATCCTCCTCCTTACCTAGACAATGAGAAGAGCAATGGAACCATTATCCATGTGAAAGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCCCTTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCTTTATTATTTTCTGGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCC.

In certain embodiments, the transmembrane domain of a presentlydisclosed CAR comprises a CD8 polypeptide. The CD8 polypeptide can havean amino acid sequence that is at least about 85%, about 90%, about 95%,about 96%, about 97%, about 98%, about 99% or 100% homologous to thesequence having a NCBI Reference No: AAH25715 (SEQ ID NO:960), orfragments thereof, and/or may optionally comprise up to one or up to twoor up to three conservative amino acid substitutions. In non-limitingembodiments, the CD8 polypeptide can have an amino acid sequence that isa consecutive portion of SEQ ID NO:960 which is at least 20, or at least30, or at least 40, or at least 50, or at least 70, or at least 100, orat least 150, or at least 200 and up to 235 amino acids in length.Alternatively or additionally, in non-limiting various embodiments, theCD8 polypeptide has an amino acid sequence of amino acids 1 to 235, 1 to50, 50 to 100, 100 to 150, 150 to 200, 130 to 210, or 200 to 235 of SEQID NO:960. In certain embodiments, the CAR of the presently disclosedsubject matter comprises a transmembrane domain comprising a CD8polypeptide. In certain embodiments, the CD8 polypeptide comprised inthe transmembrane domain has an amino acid sequence of amino acids 137to 207 of SEQ ID NO:960.

SEQ ID NO:960 is provided below:

[SEQ ID NO: 960] 1 malpvtalll plalllhaar psqfrvspld rtwnlgetvelkcqvllsnp tsgcswlfqp 61 rgaaasptfl lylsqnkpka aegldtqrfs gkrlgdtfvltlsdfrrene gcyfcsalsn 121 simyfshfvp vflpakpttt paprpptpap tiasqplslrpeacrpaagg avhtrgldfa 181 cdiyiwapla gtcgvlllsl vitlycnhrn rrrvckcprpvvksgdkpsl saryv

In accordance with the presently disclosed subject matter, a “CD8nucleic acid molecule” refers to a polynucleotide encoding a CD8polypeptide. In certain embodiments, the CD8 nucleic acid moleculeencoding the CD8 polypeptide comprised in the transmembrane domain andthe intracellular domain (e.g., the co-stimulatory signaling region) ofthe presently disclosed CAR (amino acids 137 to 207 of SEQ ID NO:960)comprises nucleic acids having the sequence set forth in SEQ ID NO:961as provided below.

[SEQ ID NO: 961] CCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCAC CCTTTACTGCAAC

In certain non-limiting embodiments, a CAR can also comprise a spacerregion that links the extracellular antigen-binding domain to thetransmembrane domain. The spacer region can be flexible enough to allowthe antigen binding domain to orient in different directions tofacilitate antigen recognition. The spacer region can be the hingeregion from IgG1, or the CH₂CH₃ region of immunoglobulin and portions ofCD3.

Intracellular Domain of a CAR

In certain non-limiting embodiments, an intracellular domain of the CARcan comprise a CD3ζ polypeptide, which can activate or stimulate a cell(e.g., a cell of the lymphoid lineage, e.g., a T cell). CD3ζ comprisesthree ITAMs, and transmits an activation signal to the cell (e.g., acell of the lymphoid lineage, e.g., a T cell) after antigen is bound.The CD3ζ polypeptide can have an amino acid sequence that is at leastabout 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about99% or about 100% homologous to the sequence set forth in SEQ ID NO:941,or fragments thereof, and/or may optionally comprise up to one or up totwo or up to three conservative amino acid substitutions. Innon-limiting embodiments, the CD3ζ polypeptide can have an amino acidsequence that is a consecutive portion of SEQ ID NO:941 which is atleast 20, or at least 30, or at least 40, or at least 50, and up to 163amino acids in length. Alternatively or additionally, in non-limitingvarious embodiments, the CD3ζ polypeptide has an amino acid sequence ofamino acids 1 to 163, 1 to 50, 50 to 100, 100 to 150, or 150 to 163 ofSEQ ID NO:941. In certain embodiments, the CD3ζ polypeptide comprised inthe intracellular domain of a presently disclosed CAR has an amino acidsequence of amino acids 52 to 163 of SEQ ID NO: 941.

SEQ ID NO: 941 is provided below:

[SEQ ID NO: 941] 1 MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILFIYGVILTALF LRVKFSRSAD 61 APAYQQGQNQ LYNELNLGRR EEYDVLDKRR GRDPEMGGKPRRKNPQEGLY NELQKDKMAE 121 AYSEIGMKGE RRRGKGHDGL YQGLSTATKD TYDALHMQALPPR

In accordance with the presently disclosed subject matter, a “CD3ζnucleic acid molecule” refers to a polynucleotide encoding a CD3ζpolypeptide. In certain embodiments, the CD3ζ nucleic acid moleculeencoding the CD3ζ polypeptide comprised in the intracellular domain of apresently disclosed CARs (amino acids 52 to 163 of SEQ ID NO: 941)comprises nucleic acids having the sequence set forth in SEQ ID NO:942as provided below.

[SEQ ID NO: 942] AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAA

In certain non-limiting embodiments, an intracellular domain of the CARfurther comprises at least one signaling region. The at least onesignaling region can include a CD28 polypeptide, a 4-1BB polypeptide, anOX40 polypeptide, an ICOS polypeptide, a DAP-10 polypeptide, a PD-1polypeptide, a CTLA-4 polypeptide, a LAG-3 polypeptide, a 2B4polypeptide, a BTLA polypeptide, a synthetic peptide (not based on aprotein associated with the immune response), or a combination thereof.

In certain embodiments, the signaling region is a co-stimulatorysignaling region. In certain embodiments, the co-stimulatory regioncomprises at least one co-stimulatory molecule, which can provideoptimal lymphocyte activation. As used herein, “co-stimulatorymolecules” refer to cell surface molecules other than antigen receptorsor their ligands that are required for an efficient response oflymphocytes to antigen. The at least one co-stimulatory signaling regioncan include a CD28 polypeptide, a 4-1BB polypeptide, an OX40polypeptide, an ICOS polypeptide, a DAP-10 polypeptide, or a combinationthereof. The co-stimulatory molecule can bind to a co-stimulatoryligand, which is a protein expressed on cell surface that upon bindingto its receptor produces a co-stimulatory response, i.e., anintracellular response that effects the stimulation provided when anantigen binds to its CAR molecule. Co-stimulatory ligands, include, butare not limited to CD80, CD86, CD70, OX40L, 4-1BBL, CD48, TNFRSF14, andPD-L1. As one example, a 4-1BB ligand (i.e., 4-1BBL) may bind to 4-1BB(also known as “CD137”) for providing an intracellular signal that incombination with a CAR signal induces an effector cell function of theCAR⁺ T cell. CARs comprising an intracellular domain that comprises aco-stimulatory signaling region comprising 4-1BB, ICOS or DAP-10 aredisclosed in U.S. Pat. No. 7,446,190 (e.g., the nucleotide sequenceencoding 4-1BB is set forth in SEQ ID NO:15, the nucleotide sequenceencoding ICOS is set forth in SEQ ID NO:16, and the nucleotide sequenceencoding DAP-10 is set forth in SEQ ID NO:17 in U.S. Pat. No.7,446,190), which is herein incorporated by reference in its entirety.In certain embodiments, the intracellular domain of the CAR comprises aco-stimulatory signaling region that comprises a CD28 polypeptide. Incertain embodiments, the intracellular domain of the CAR comprises aco-stimulatory signaling region that comprises two co-stimulatorymolecules:CD28 and 4-1BB or CD28 and OX40.

4-1BB can act as a tumor necrosis factor (TNF) ligand and havestimulatory activity. The 4-1BB polypeptide can have an amino acidsequence that is at least about 85%, about 90%, about 95%, about 96%,about 97%, about 98%, about 99% or 100% homologous to the sequencehaving a NCBI Reference No: P41273 or NP_001552 (SEQ ID NO:943) orfragments thereof, and/or may optionally comprise up to one or up to twoor up to three conservative amino acid substitutions. In certainembodiments, the 4-1BB polypeptide comprised in the intracellular domainof a presently disclosed CAR has an amino acid sequence of amino acids214 to 255 of SEQ ID NO: 943. SEQ ID NO:943 is provided below:

[SEQ ID NO: 943] 1MGNSCYNIVA TLLLVLNFER TRSLQDPCSN CPAGTFCDNN RNQICSPCPP NSFSSAGGQR 61TCDICRQCKG VFRTRKECSS TSNAECDCTP GFHCLGAGCS MCEQDCKQGQ ELTKKGCKDC 121CFGTFNDQKR GICRPWTNCS LDGKSVLVNG TKERDVVCGP SPADLSPGAS SVTPPAPARE 181PGHSPQIISF FLALTSTALL FLLFFLTLRF SVVKRGRKKL LYIFKQPFMR PVQTTQEEDG 241CSCRFPEEEE GGCEL

In accordance with the presently disclosed subject matter, a “4-1BBnucleic acid molecule” refers to a polynucleotide encoding a 4-1BBpolypeptide. In certain embodiments, the 4-1BB nucleic acid moleculeencoding the 4-1BB polypeptide comprised in the intracellular domain ofa presently disclosed CARs (amino acids 214 to 255 of SEQ ID NO: 943)comprises nucleic acids having the sequence set forth in SEQ ID NO: 962as provided below.

[SEQ ID NO: 962] AAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTG

An OX40 polypeptide can have an amino acid sequence that is at leastabout 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about99% or 100% homologous to the sequence having a NCBI Reference No:P43489 or NP_003318 (SEQ ID NO:944), or fragments thereof, and/or mayoptionally comprise up to one or up to two or up to three conservativeamino acid substitutions.

SEQ ID NO:944 is provided below:

[SEQ ID NO: 944] 1MCVGARRLGR GPCAALLLLG LGLSTVTGLH CVGDTYPSND RCCHECRPGN GMVSRCSRSQ 61NTVCRPCGPG FYNDVVSSKP CKPCTWCNLR SGSERKQLCT ATQDTVCRCR AGTQPLDSYK 121PGVDCAPCPP GHFSPGDNQA CKPWTNCTLA GKHTLQPASN SSDAICEDRD PPATQPQETQ 181GPPARPITVQ PTEAWPRTSQ GPSTRPVEVP GGRAVAAILG LGLVLGLLGP LAILLALYLL 241RRDQRLPPDA HKPPGGGSFR TPIQEEQADA HSTLAKI

In accordance with the presently disclosed subject matter, an “OX40nucleic acid molecule” refers to a polynucleotide encoding an OX40polypeptide.

An ICOS polypeptide can have an amino acid sequence that is at leastabout 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about99% or 100% homologous to the sequence having a NCBI Reference No:NP_036224 (SEQ ID NO:945) or fragments thereof, and/or may optionallycomprise up to one or up to two or up to three conservative amino acidsubstitutions.

SEQ ID NO:945 is provided below:

[SEQ ID NO: 945] 1MKSGLWYFFL FCLRIKVLTG EINGSANYEM FIFHNGGVQI LCKYPDIVQQ FKMQLLKGGQ 61ILCDLTKTKG SGNTVSIKSL KFCHSQLSNN SVSFFLYNLD HSHANYYFCN LSIFDPPPFK 121VTLTGGYLHI YESQLCCQLK FWLPIGCAAF VVVCILGCIL ICWLTKKKYS SSVHDPNGEY 181MFMRAVNTAK KSRLTDVTL

In accordance with the presently disclosed subject matter, an “ICOSnucleic acid molecule” refers to a polynucleotide encoding an ICOSpolypeptide.

CTLA-4 is an inhibitory receptor expressed by activated T cells, whichwhen engaged by its corresponding ligands (CD80 and CD86; B7-1 and B7-2,respectively), mediates activated T cell inhibition or anergy. In bothpreclinical and clinical studies, CTLA-4 blockade by systemic antibodyinfusion, enhanced the endogenous anti-tumor response albeit, in theclinical setting, with significant unforeseen toxicities.

CTLA-4 contains an extracellular V domain, a transmembrane domain, and acytoplasmic tail. Alternate splice variants, encoding differentisoforms, have been characterized. The membrane-bound isoform functionsas a homodimer interconnected by a disulfide bond, while the solubleisoform functions as a monomer. The intracellular domain is similar tothat of CD28, in that it has no intrinsic catalytic activity andcontains one YVKM motif able to bind PI3K, PP2A and SHP-2 and oneproline-rich motif able to bind SH3 containing proteins. One role ofCTLA-4 in inhibiting T cell responses seem to be directly via SHP-2 andPP2A dephosphorylation of TCR-proximal signaling proteins such as CD3and LAT. CTLA-4 can also affect signaling indirectly via competing withCD28 for CD80/86 binding. CTLA-4 has also been shown to bind and/orinteract with PI3K, CD80, AP2M1, and PPP2R5A.

In accordance with the presently disclosed subject matter, a CTLA-4polypeptide can have an amino acid sequence that is at least about 85%,about 90%, about 95%, about 96%, about 97%, about 98%, about 99% orabout 100% homologous to UniProtKB/Swiss-Prot Ref. No.: P16410.3 (SEQ IDNO:946) (homology herein may be determined using standard software suchas BLAST or FASTA) or fragments thereof, and/or may optionally compriseup to one or up to two or up to three conservative amino acidsubstitutions.

SEQ ID NO:946 is provided below:

[SEQ ID NO: 946] 1MACLGFQRHK AQLNLATRTW PCTLLFFLLF IPVFCKAMHV AQPAVVLASS RGIASFVCEY 61ASPGKATEVR VTVLRQADSQ VTEVCAATYM MGNELTFLDD SICTGTSSGN QVNLTIQGLR 121AMDTGLYICK VELMYPPPYY LGIGNGTQIY VIDPEPCPDS DFLLWILAAV SSGLFFYSFL 181LTAVSLSKML KKRSPLTTGV YVKMPPTEPE CEKQFQPYFI PIN

In accordance with the presently disclosed subject matter, a “CTLA-4nucleic acid molecule” refers to a polynucleotide encoding a CTLA-4polypeptide.

PD-1 is a negative immune regulator of activated T cells upon engagementwith its corresponding ligands PD-L1 and PD-L2 expressed on endogenousmacrophages and dendritic cells. PD-1 is a type I membrane protein of268 amino acids. PD-1 has two ligands, PD-L1 and PD-L2, which aremembers of the B7 family. The protein's structure comprises anextracellular IgV domain followed by a transmembrane region and anintracellular tail. The intracellular tail contains two phosphorylationsites located in an immunoreceptor tyrosine-based inhibitory motif andan immunoreceptor tyrosine-based switch motif, that PD-1 negativelyregulates TCR signals. SHP-I and SHP-2 phosphatases bind to thecytoplasmic tail of PD-1 upon ligand binding. Upregulation of PD-L1 isone mechanism tumor cells may evade the host immune system. Inpre-clinical and clinical trials, PD-1 blockade by antagonisticantibodies induced anti-tumor responses mediated through the hostendogenous immune system.

In accordance with the presently disclosed subject matter, a PD-1polypeptide can have an amino acid sequence that is at least about 85%,about 90%, about 95%, about 96%, about 97%, about 98%, about 99% orabout 100% homologous to NCBI Reference No: NP_005009.2 (SEQ ID NO:947)or fragments thereof, and/or may optionally comprise up to one or up totwo or up to three conservative amino acid substitutions. SEQ ID NO:947is provided below:

[SEQ ID NO: 947] 1MQIPQAPWPV VWAVLQLGWR PGWFLDSPDR PWNPPTFSPA LLVVTEGDNA TFTCSFSNTS 61ESFVLNWYRM SPSNQTDKLA AFPEDRSQPG QDCRFRVTQL PNGRDFHMSV VRARRNDSGT 121YLCGAISLAP KAQIKESLRA ELRVTERRAE VPTAHPSPSP RPAGQFQTLV VGVVGGLLGS 181LVLLVWVLAV ICSRAARGTI GARRTGQPLK EDPSAVPVFS VDYGELDFQW REKTPEPPVP 241CVPEQTEYAT IVFPSGMGTS SPARRGSADG PRSAQPLRPE DGHCSWPL

In accordance with the presently disclosed subject matter, a “PD-1nucleic acid molecule” refers to a polynucleotide encoding a PD-1polypeptide.

Lymphocyte-activation protein 3 (LAG-3) is a negative immune regulatorof immune cells. LAG-3 belongs to the immunoglobulin (lg) superfamilyand contains 4 extracellular Ig-like domains. The LAG3 gene contains 8exons. The sequence data, exon/intron organization, and chromosomallocalization all indicate a close relationship of LAG3 to CD4. LAG3 hasalso been designated CD223 (cluster of differentiation 223).

In accordance with the the presently disclosed subject matter, a LAG-3polypeptide can have an amino acid sequence that is at least about 85%,about 90%, about 95%, about 96%, about 97%, about 98%, about 99% orabout 100% homologous to UniProtKB/Swiss-Prot Ref. No.: P18627.5 (SEQ IDNO:948) or fragments thereof, and/or may optionally comprise up to oneor up to two or up to three conservative amino acid substitutions.

SEQ ID NO:948 is provided below:

[SEQ ID NO: 948] 1MWEAQFLGLL FLQPLWVAPV KPLQPGAEVP VVWAQEGAPA QLPCSPTIPL QDLSLLRRAG 61VTWQHQPDSG PPAAAPGHPL APGPHPAAPS SWGPRPRRYT VLSVGPGGLR SGRLPLQPRV 121QLDERGRQRG DFSLWLRPAR RADAGEYRAA VHLRDRALSC RLRLRLGQAS MTASPPGSLR 181ASDWVILNCS FSRPDRPASV HWFRNRGQGR VPVRESPHHH LAESFLFLPQ VSPMDSGPWG 241CILTYRDGFN VSIMYNLTVL GLEPPTPLTV YAGAGSRVGL PCRLPAGVGT RSFLTAKWTP 301PGGGPDLLVT GDNGDFTLRL EDVSQAQAGT YTCHIHLQEQ QLNATVTLAI ITVTPKSFGS 361PGSLGKLLCE VTPVSGQERF VWSSLDTPSQ RSFSGPWLEA QEAQLLSQPW QCQLYQGERL 421LGAAVYFTEL SSPGAQRSGR APGALPAGHL LLFLILGVLS LLLLVTGAFG FHLWRRQWRP 481RRFSALEQGI HPPQAQSKIE ELEQEPEPEP EPEPEPEPEP EPEQL

In accordance with the presently disclosed subject matter, a “LAG-3nucleic acid molecule” refers to a polynucleotide encoding a LAG-3polypeptide.

Natural Killer Cell Receptor 2B4 (2B4) mediates non-MHC restricted cellkilling on NK cells and subsets of T cells. To date, the function of 2B4is still under investigation, with the 2B4-S isoform believed to be anactivating receptor, and the 2B4-L isoform believed to be a negativeimmune regulator of immune cells. 2B4 becomes engaged upon binding itshigh-affinity ligand, CD48. 2B4 contains a tyrosine-based switch motif,a molecular switch that allows the protein to associate with variousphosphatases. 2B4 has also been designated CD244 (cluster ofdifferentiation 244).

In accordance with the presently disclosed subject matter, a 2B4polypeptide can have an amino acid sequence that is at least about 85%,about 90%, about 95%, about 96%, about 97%, about 98%, about 99% orabout 100% homologous to UniProtKB/Swiss-Prot Ref. No.: Q9BZW8.2 (SEQ IDNO:949) or fragments thereof, and/or may optionally comprise up to oneor up to two or up to three conservative amino acid substitutions.

SEQ ID NO:949 is provided below:

[SEQ ID NO: 949] 1MLGQVVTLIL LLLLKVYQGK GCQGSADHVV SISGVPLQLQ PNSIQTKVDS IAWKKLLPSQ 61NGFHHILKWE NGSLPSNTSN DRFSFIVKNL SLLIKAAQQQ DSGLYCLEVT SISGKVQTAT 121FQVFVFESLL PDKVEKPRLQ GQGKILDRGR CQVALSCLVS RDGNVSYAWY RGSKLIQTAG 181NLTYLDEEVD INGTHTYTCN VSNPVSWESH TLNLTQDCQN AHQEFRFWPF LVIIVILSAL 241FLGTLACFCV WRRKRKEKQS ETSPKEFLTI YEDVKDLKTR RNHEQEQTFP GGGSTIYSMI 301QSQSSAPTSQ EPAYTLYSLI QPSRKSGSRK RNHSPSFNST IYEVIGKSQP KAQNPARLSR 361KELENFDVYS

In accordance with the presently disclosed subject matter, a “2B4nucleic acid molecule” refers to a polynucleotide encoding a 2B4polypeptide.

B- and T-lymphocyte attenuator (BTLA) expression is induced duringactivation of T cells, and BTLA remains expressed on Th1 cells but notTh2 cells. Like PD1 and CTLA4, BTLA interacts with a B7 homolog, B7H4.However, unlike PD-1 and CTLA-4, BTLA displays T-Cell inhibition viainteraction with tumor necrosis family receptors (TNF-R), not just theB7 family of cell surface receptors. BTLA is a ligand for tumor necrosisfactor (receptor) superfamily, member 14 (TNFRSF14), also known asherpes virus entry mediator (HVEM). BTLA-HVEM complexes negativelyregulate T-cell immune responses. BTLA activation has been shown toinhibit the function of human CD8⁺ cancer-specific T cells. BTLA hasalso been designated as CD272 (cluster of differentiation 272).

In accordance with the presently disclosed subject matter, a BTLApolypeptide can have an amino acid sequence that is at least about 85%,about 90%, about 95%, about 96%, about 97%, about 98%, about 99% orabout 100% homologous to UniProtKB/Swiss-Prot Ref. No.: Q7Z6A9.3 (SEQ IDNO:950) or fragments thereof, and/or may optionally comprise up to oneor up to two or up to three conservative amino acid substitutions.

SEQ ID NO:950 is provided below:

[SEQ ID NO: 950] 1MKTLPAMLGT GKLFWVFFLI PYLDIWNIHG KESCDVQLYI KRQSEHSILA GDPFELECPV 61KYCANRPHVT WCKLNGTTCV KLEDRQTSWK EEKNISFFIL HFEPVLPNDN GSYRCSANFQ 121SNLIESHSTT LYVTDVKSAS ERPSKDEMAS RPWLLYRLLP LGGLPLLITT CFCLFCCLRR 181HQGKQNELSD TAGREINLVD AHLKSEQTEA STRQNSQVLL SETGIYDNDP DLCFRMQEGS 241EVYSNPCLEE NKPGIVYASL NHSVIGPNSR LARNVKEAPT EYASICVRS

In accordance with the presently disclosed subject matter, a “BTLAnucleic acid molecule” refers to a polynucleotide encoding a BTLApolypeptide.

In certain embodiments, the CAR comprises an extracellularantigen-binding region that specifically binds to human FcRL5, atransmembrane domain comprising a CD28 polypeptide, and an intracellulardomain comprising a CD3ζ polypeptide and a co-stimulatory signalingregion that comprises a CD28 polypeptide, as shown in FIG. 9. As shownin FIG. 9, the CAR also comprises a signal peptide or a leadercovalently joined to the 5′ terminus of the extracellularantigen-binding domain. The signal peptide comprises a CD8 polypeptide.

In certain embodiments, the CAR of the presently disclosed subjectmatter can further comprise an inducible promoter, for expressingnucleic acid sequences in human cells. Promoters for use in expressingCAR genes can be a constitutive promoter, such as ubiquitin C (UbiC)promoter.

The presently disclosed subject matter also provides isolated nucleicacid molecule encoding the FcRL5-targeted CAR described herein or afunctional portion thereof. In certain embodiments, the isolated nucleicacid molecule encodes a presently disclosed FcRL5-targeted CARcomprising an scFv that specifically binds to human FcRL5, atransmembrane domain comprising a CD28 polypeptide, and an intracellulardomain comprising a CD3ζ polypeptide and a co-stimulatory signalingregion comprising a CD28 polypeptide. In certain embodiments, the scFvis a fully human scFv. In certain embodiments, the scFv is a murinescFv. In certain non-limiting embodiments, the isolated nucleic acidmolecule comprises nucleic acids having the sequence set forth in SEQ IDNO:951 provided below:

[SEQ ID NO: 951] ATGGCTCTCCCAGTGACTGCCCTACTGCTTCCCCTAGCGCTTCTCCTGCATGCAGCTCGTGTGAAGCTGCAGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCGGAAACTCTCCTGTGCAGCCTCTGGATTCACTTTCAGTATCTTTGGATTGCACTGGGTTCGTCAGGCTCCAGAGAAGGGGCTGGAGTGGGTCGCATACATTAGTGGTGACAGTAATACCATCTACTATGCAGACACAGTGAAGGGCCGATTCACCATCTCCAGAGACAATCCCAAGAACACCCTGTTCCTGCAAATGACCAGTCTAAGGTCTGAGGACACGGCCATGTATTACTGTGCAAGAAATAGCTACTATGCTCTGGACTACTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGGTGGAGGTGGATCAGGTGGAGGTGGATCTGGTGGAGGTGGATCTGACATTGAGCTCACCCAGTCTCCAGCAATCATGTCTGTATCTCCAGGTGAAAAGGTCACCATGACCTGCAGGGCCAGCTCAAGTGTCAGTTCCAGTTACTTGCACTGGTACCAGCAGAGGTCAGGTGCCTCCCCCAAAATCTGGATTTATAGCACATCCAACTTGGCTTCTGGAGTCCCTGCTCGCTTCAGTGGCAGTGGGACTGGGACCTCTTACTCTCTCACAATCAGCAGTGTGGAGGCTGAAGATGCTGCCACTTATTACTGCCAGCAGTACAGTGGTTACCCGTGGACGTTCGGTGGAGGGACCAAGCTGGAGATCGAACAAAAACTCATCTCAGAAGAGGATCTGGCGGCCGCAATTGAAGTTATGTATCCTCCTCCTTACCTAGACAATGAGAAGAGCAATGGAACCATTATCCATGTGAAAGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCCCTTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCTTTATTATTTTCTGGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAA

The isolated nucleic acid molecule having the nucleotide sequence of SEQID NO:951 encodes a FcRL-5-targeted CAR comprising a murine scFv thatcomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:915, a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:917,and a linker having an amino acid sequence of SEQ ID NO:897 positionedbetween the heavy chain variable region and the light chain variableregion, a transmembrane domain comprising a CD28 polypeptide, and anintracellular domain comprising a CD3ζ polypeptide and a co-stimulatorysignaling region comprising a CD28 polypeptide.

In another specific non-limiting example, the isolated nucleic acidmolecule comprises nucleic acids having the sequence set forth in SEQ IDNO:952 provided below:ATGGAGACAGACACACTCCTGCTATGGGTACTGCTGCTCTGGGTTCCAGGTTCCACTGGTGACGTCCAACTGCAGGAGTCAGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCGGAAACTCTCCTGTACAGCCTCTGGATTCACTTTCAGTAGCTTTGGAATGCACTGGGTTCGTCAGGCTCCAGAGAAGGGGCTGGAGTGGGTCGCATACATTAGTAGTGGCAGTAATAACATCTACTTTGCGGACACAGTGAAGGGCCGATTCACCATCTCCAGAGACAATCCCAAGAACACCCTGTTCCTGCAAATGACCAGTCTAAGGTCTGAGGACACGGCCATGTATTACTGTGCAAGATCGGAATACTACGGTAGTAGCCATATGGACTACTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGGTGGAGGTGGATCAGGTGGAGGTGGATCTGGTGGAGGTGGATCTGACATTGAGCTCACCCAGTCTCCAAAATTCATGTCCACATCAGTAGGAGACAGGGTCAGCGTCACCTGCAAGGCCAGTCAGAATGTGGGTACTAATGTAGCCTGGTATCAACAGAAACCAGGACAATCTCCTAAACCACTGATTTACTCGGCAACCTACCGGAACAGTGGAGTCCCTGATCGCTTCACAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCACTAACGTGCAGTCTAAAGACTTGGCAGACTATTTCTGTCAACAATATAACAGGTATCCGTACACGTCCGGAGGGGGGACCAAGCTGGAGATCGAACAAAAACTCATCTCAGAAGAGGATCTGGCGGCCGCAATTGAAGTTATGTATCCTCCTCCTTACCTAGACAATGAGAAGAGCAATGGAACCATTATCCATGTGAAAGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCCCTTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCTTTATTATTTTCTGGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAA [SEQ IDNo: 952]. The isolated nucleic acid molecule having the nucleotidesequence of SEQ ID NO:952 encodes a FcRL-5-targeted CAR comprising amurine scFv that comprises a heavy chain variable region comprisingamino acids having the sequence set forth in SEQ ID NO:919, a lightchain variable region comprising amino acids having the sequence setforth in SEQ ID NO:921, and a linker having an amino acid sequence ofSEQ ID NO:897 positioned between the heavy chain variable region and thelight chain variable region, a transmembrane domain comprising a CD28polypeptide, and an intracellular domain comprising a CD3ζ polypeptideand a co-stimulatory signaling region comprising a CD28 polypeptide.

In certain embodiments, the isolated nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:953 providedbelow:CCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGCCATGGAAACCGATACACTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGCTCCTATGTGCTGACTCAGCCACCCTCAGTGTCAGTGGCCCCAGGAAAGACGGCCAGGATTACCTGTGGGGGAAACAACATTGGAAGTAAAAGTGTGCACTGGTACCAGCAGAAGCCAGGCCAGGCCCCTGTGCTGGTCATCTATTATGATAGCGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCTCCAACTCTGGGAACACGGCCACCCTGACCATCAGCAGGGTCGAAGCCGGGGATGAGGCCGACTATTACTGTCAGGTGTGGGATAGTAGTAGTGATTATGTCTTCGGAACTGGGACCAAGGTCACCGTCCTAGGTTCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCCGAGGTGCAGCTGGTGGAGACTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCGTCAGTGACTACTACATGAGCTGGATCCGCCAGGCTCCAGGGAAGGGCCTGGAGTGGATTTCATACATTAGTGGTAGTGGTAATAGCATATACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGGGACAACGCCAAGAACTCACTGGATCTGCAAATGACCAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGCGCTCTACTAAATTCGATTACTGGGGTCAAGGTACTCTGGTGACCGTCTCCTCAGCGGCCGCACCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACAAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGAGCCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAACAGCCACTCGAGGATCCGGATTAGTCCAATTTGTTAAAGACAGGATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTACGAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCACACATGCAGCATGTATCAAAATTAATTTGGTTTTTTTTCTTAAGTATTTACATTAAATGGCCATAGTACTTAAAGTTACATTGGCTTCCTTGAAATAAACATGGAGTATTCAGAATGTGTCATAAATATTTCTAATTTTAAGATAGTATCTCCATTGGCTTTCTACTTTTTCTTTTATTTTTTTTTGTCCTCTGTCTTCCATTTGTTGTTGTTGTTGTTTGTTTGTTTGTTTGTTGGTTGGTTGGTTAATTTTTTTTTAAAGATCCTACACTATAGTTCAAGCTAGACTATTAGCTACTCTGTAACCCAGGGTGACCTTGAAGTCATGGGTAGCCTGCTGTTTTAGCCTTCCCACATCTAAGATTACAGGTATGAGCTATCATTTTTGGTATATTGATTGATTGATTGATTGATGTGTGTGTGTGTGATTGTGTTTGTGTGTGTGACTGTGAAAATGTGTGTATGGGTGTGTGTGAATGTGTGTATGTATGTGTGTGTGTGAGTGTGTGTGTGTGTGTGTGCATGTGTGTGTGTGTGACTGTGTCTATGTGTATGACTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGTGAAAAAATATTCTATGGTAGTGAGAGCCAACGCTCCGGCTCAGGTGTCAGGTTGGTTTTTGAGACAGAGTCTTTCACTTAGCTTGGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGATGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCATTGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTGCTCTTAGGAGTTTCCTAATACATCCCAAACTCAAATATATAAAGCATTTGACTTGTTCTATGCCCTAGGGGGCGGGGGGAAGCTAAGCCAGCTTTTTTTAACATTTAAAATGTTAATTCCATTTTAAATGCACAGATGTTTTTATTTCATAAGGGTTTCAATGTGCATGAATGCTGCAATATTCCTGTTACCAAAGCTAGTATAAATAAAAATAGATAAACGTGGAAATTACTTAGAGTTTCTGTCATTAACGTTTCCTTCCTCAGTTGACAACATAAATGCGCTGCTGAGCAAGCCAGTTTGCATCTGTCAGGATCAATTTCCCATTATGCCAGTCATATTAATTACTAGTCAATTAGTTGATTTTTATTTTTGACATATACATGTGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGACCACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGTGTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGACTTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGTGCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCTAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCAAGAACAACTGGACCGA [SEQ ID No: 953]. The isolated nucleic acidmolecule having the nucleotide sequence of SEQ ID NO:953 encodes aFcRL-5-targeted CAR (designated as 31 FcRL5-targeted BBz CAR) comprisinga fully human scFv (encoded by nucleotides 207-998 of SEQ ID NO:953)that comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:116, a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:115, and a linker having an amino acid sequence of SEQ ID NO:307positioned between the heavy chain variable region and the light chainvariable region, a transmembrane domain comprising a CD8 polypeptidehaving 137 to 207 of SEQ ID NO: 960, and an intracellular domaincomprising a CD3ζ polypeptide comprising amino acids 52 to 163 of SEQ IDNO: 941, and a co-stimulatory signaling region comprising a 4-1BBpolypeptide having amino acids 214-255 of SEQ ID NO: 943. Nucleotides270-998 of SEQ ID NO: 953 encodes the human scFv. Nucleotides 1008-1220of SEQ ID NO: 953 encodes the CD8 polypeptide comprised in thetransmembrane domain. Nucleotides 1221-1346 of SEQ ID NO: 953 encodesthe 4-1BB polypeptide comprised in the intracellular domain. Nucleotides1347-1685 of SEQ ID NO: 953 encodes the CD3zeta polypeptide comprised inthe intracellular domain. Other portions of SEQ ID NO: 953 are shown inTable 232.

TABLE 232 Nucleotide Sequence Positions Number of Portions of SEQ ID NO:953 Nucleotides anti-FcRL5 scFv 31 207 . . . 998 792 CD8a TM 1008 . . .1220 213 4-1BB 1221 . . . 1346 126 CD3zeta 1347 . . . 1685 339 LTR 1965. . . 2434 470 M13 fwd 3133 . . . 3149 17 AmpR promoter 3624 . . . 3728105 AmpR 3729 . . . 4589 861 ori 4760 . . . 5348 589 CAP binding site5636 . . . 5657 22 lac promoter 5672 . . . 5702 31 lac operator 5710 . .. 5726 17 M13 rev 5734 . . . 5750 17 LTR 6159 . . . 6752 594 MMLV Psi6815 . . . 7172 358 gag (truncated) 7237 . . . 7653 417

In certain embodiments, the isolated nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:954 providedbelow:CCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGCCATGGAAACCGATACACTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGCAATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCCGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTTCCCCCACCACTGTGATCTATGAGGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATAGCAGCAATTGGGTGTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTTCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCCGAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGGATCATCCCTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGCGCTCTAACTACTACTACAACGATTACTGGGGTCAAGGTACTCTGGTGACCGTCTCCTCAGCGGCCGCACCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACAAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGAGCCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAACAGCCACTCGAGGATCCGGATTAGTCCAATTTGTTAAAGACAGGATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTACGAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCACACATGCAGCATGTATCAAAATTAATTTGGTTTTTTTTCTTAAGTATTTACATTAAATGGCCATAGTACTTAAAGTTACATTGGCTTCCTTGAAATAAACATGGAGTATTCAGAATGTGTCATAAATATTTCTAATTTTAAGATAGTATCTCCATTGGCTTTCTACTTTTTCTTTTATTTTTTTTTGTCCTCTGTCTTCCATTTGTTGTTGTTGTTGTTTGTTTGTTTGTTTGTTGGTTGGTTGGTTAATTTTTTTTTAAAGATCCTACACTATAGTTCAAGCTAGACTATTAGCTACTCTGTAACCCAGGGTGACCTTGAAGTCATGGGTAGCCTGCTGTTTTAGCCTTCCCACATCTAAGATTACAGGTATGAGCTATCATTTTTGGTATATTGATTGATTGATTGATTGATGTGTGTGTGTGTGATTGTGTTTGTGTGTGTGACTGTGAAAATGTGTGTATGGGTGTGTGTGAATGTGTGTATGTATGTGTGTGTGTGAGTGTGTGTGTGTGTGTGTGCATGTGTGTGTGTGTGACTGTGTCTATGTGTATGACTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGTGAAAAAATATTCTATGGTAGTGAGAGCCAACGCTCCGGCTCAGGTGTCAGGTTGGTTTTTGAGACAGAGTCTTTCACTTAGCTTGGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGATGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCATTGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTGCTCTTAGGAGTTTCCTAATACATCCCAAACTCAAATATATAAAGCATTTGACTTGTTCTATGCCCTAGGGGGCGGGGGGAAGCTAAGCCAGCTTTTTTTAACATTTAAAATGTTAATTCCATTTTAAATGCACAGATGTTTTTATTTCATAAGGGTTTCAATGTGCATGAATGCTGCAATATTCCTGTTACCAAAGCTAGTATAAATAAAAATAGATAAACGTGGAAATTACTTAGAGTTTCTGTCATTAACGTTTCCTTCCTCAGTTGACAACATAAATGCGCTGCTGAGCAAGCCAGTTTGCATCTGTCAGGATCAATTTCCCATTATGCCAGTCATATTAATTACTAGTCAATTAGTTGATTTTTATTTTTGACATATACATGTGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGACCACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGTGTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGACTTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGTGCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCTAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCAAGAACAACTGGACCGA [SEQ ID NO: 954]. The isolatednucleic acid molecule having the nucleotide sequence of SEQ ID NO:954encodes a FcRL-5-targeted CAR (designated as 39 FcRL5-targeted BBz CAR)comprising a fully human scFv (encoded by nucleotides 207-1013 of SEQ IDNO:954) that comprises a heavy chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:144, a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:143, and a linker having an amino acid sequence of SEQ IDNO:307 positioned between the heavy chain variable region and the lightchain variable region, a transmembrane domain comprising a CD8polypeptide having 137 to 207 of SEQ ID NO: 960, and an intracellulardomain comprising a CD3ζ polypeptide comprising amino acids 52 to 163 ofSEQ ID NO: 941, and a co-stimulatory signaling region comprising a 4-1BBpolypeptide having amino acids 214-255 of SEQ ID NO: 943. Nucleotides207-1013 of SEQ ID NO: 954 encodes the human scFv. Nucleotides 1023-1235of SEQ ID NO: 954 encodes the CD8 polypeptide comprised in thetransmembrane domain. Nucleotides 1236-1361 of SEQ ID NO: 954 encodesthe 4-1BB polypeptide comprised in the intracellular domain. Nucleotides1362-1700 of SEQ ID NO: 954 encodes the CD3zeta polypeptide comprised inthe intracellular domain. Other portions of SEQ ID NO: 954 are shown inTable 233.

TABLE 233 Nucleotide Sequence Positions of SEQ ID NO: Portions 954Number of Nucleotides anti-FcRL5 scFv 39  207 . . . 1013 807 CD8a TM1023 . . . 1235 213 4-1BB 1236 . . . 1361 126 CD3zeta 1362 . . . 1700339 LTR 1980 . . . 2449 470 M13 fwd 3148 . . . 3164 17 AmpR promoter3639 . . . 3743 105 AmpR 3744 . . . 4604 861 ori 4775 . . . 5363 589 CAPbinding site 5651 . . . 5672 22 lac promoter 5687 . . . 5717 31 lacoperator 5725 . . . 5741 17 M13 rev 5749 . . . 5765 17 LTR 6174 . . .6767 594 MMLV Psi 6830 . . . 7187 358 gag (truncated) 7252 . . . 7668417

In certain embodiments, the isolated nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:955 providedbelow:CCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGCCATGGAAACCGACACCCTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGACAGTCTGTCGTGACGCAGCCACCCTCAGCGTCTGGGACCCCCGGGCAGAGGGTCACCATCTCTTGTTCTGGAAGCAGCTCCAACATCGGAAGTAATTATGTATACTGGTACCAGCAGCTCCCAGGAACGGCCCCCAAACTCCTCATCTATAGTAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGATGAGGCTGATTATTACTGTGCAGCATGGGATGACAGCCTGAGTGGTTATGTCTTCGGAACTGGGACCAAGCTGACCGTCCTAGGTTCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCCCAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCTCACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCCCCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCCGTGTATTACTGTGCGCGCCTGTACGAAGGTGGTTACCATGGTTGGGGTTCTTGGCTGTCTTCTGATTCTTGGGGTCAAGGTACTCTGGTGACCGTCTCCTCAGCGGCCGCACCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACAAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGAGCCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAACAGCCACTCGAGGATCCGGATTAGTCCAATTTGTTAAAGACAGGATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTACGAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCACACATGCAGCATGTATCAAAATTAATTTGGTTTTTTTTCTTAAGTATTTACATTAAATGGCCATAGTACTTAAAGTTACATTGGCTTCCTTGAAATAAACATGGAGTATTCAGAATGTGTCATAAATATTTCTAATTTTAAGATAGTATCTCCATTGGCTTTCTACTTTTTCTTTTATTTTTTTTTGTCCTCTGTCTTCCATTTGTTGTTGTTGTTGTTTGTTTGTTTGTTTGTTGGTTGGTTGGTTAATTTTTTTTTAAAGATCCTACACTATAGTTCAAGCTAGACTATTAGCTACTCTGTAACCCAGGGTGACCTTGAAGTCATGGGTAGCCTGCTGTTTTAGCCTTCCCACATCTAAGATTACAGGTATGAGCTATCATTTTTGGTATATTGATTGATTGATTGATTGATGTGTGTGTGTGTGATTGTGTTTGTGTGTGTGACTGTGAAAATGTGTGTATGGGTGTGTGTGAATGTGTGTATGTATGTGTGTGTGTGAGTGTGTGTGTGTGTGTGTGCATGTGTGTGTGTGTGACTGTGTCTATGTGTATGACTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGTGAAAAAATATTCTATGGTAGTGAGAGCCAACGCTCCGGCTCAGGTGTCAGGTTGGTTTTTGAGACAGAGTCTTTCACTTAGCTTGGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGATGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCATTGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTGCTCTTAGGAGTTTCCTAATACATCCCAAACTCAAATATATAAAGCATTTGACTTGTTCTATGCCCTAGGGGGCGGGGGGAAGCTAAGCCAGCTTTTTTTAACATTTAAAATGTTAATTCCATTTTAAATGCACAGATGTTTTTATTTCATAAGGGTTTCAATGTGCATGAATGCTGCAATATTCCTGTTACCAAAGCTAGTATAAATAAAAATAGATAAACGTGGAAATTACTTAGAGTTTCTGTCATTAACGTTTCCTTCCTCAGTTGACAACATAAATGCGCTGCTGAGCAAGCCAGTTTGCATCTGTCAGGATCAATTTCCCATTATGCCAGTCATATTAATTACTAGTCAATTAGTTGATTTTTATTTTTGACATATACATGTGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGACCACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGTGTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGACTTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGTGCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCTAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCAAGAACAACTGGACCGA [SEQ IDNO: 955]. The isolated nucleic acid molecule having the nucleotidesequence of SEQ ID NO:955 encodes a FcRL-5-targeted CAR (designated as69 FcRL5-targeted BBz CAR) comprising a fully human scFv (encoded bynucleotides 207-1037 of SEQ ID NO:955) that comprises a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:172, a light chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:171, and a linker having anamino acid sequence of SEQ ID NO:307 positioned between the heavy chainvariable region and the light chain variable region, a transmembranedomain comprising a CD8 polypeptide having 137 to 207 of SEQ ID NO: 960,and an intracellular domain comprising a CD3ζ polypeptide comprisingamino acids 52 to 163 of SEQ ID NO: 941, and a co-stimulatory signalingregion comprising a 4-1BB polypeptide having amino acids 214-255 of SEQID NO: 943. Nucleotides 207-1037 of SEQ ID NO: 955 encodes the humanscFv. Nucleotides 1047-1259 of SEQ ID NO: 955 encodes the CD8polypeptide comprised in the transmembrane domain. Nucleotides 1260-1385of SEQ ID NO: 955 encodes the 4-1BB polypeptide comprised in theintracellular domain. Nucleotides 1386-1724 of SEQ ID NO: 955 encodesthe CD3zeta polypeptide comprised in the intracellular domain. Otherportions of SEQ ID NO: 955 are shown in Table 234.

TABLE 234 Nucleotide Sequence Positions of SEQ ID NO: Portions 955Number of Nucleotides anti-FcRL5 scFv 69  207 . . . 1037 831 CD8a TM1047 . . . 1259 213 4-1BB 1260 . . . 1385 126 CD3zeta 1386 . . . 1724339 LTR 2004 . . . 2473 470 M13 fwd 3172 . . . 3188 17 AmpR promoter3663 . . . 3767 105 AmpR 3768 . . . 4628 861 ori 4799 . . . 5387 589 CAPbinding site 5675 . . . 5696 22 lac promoter 5711 . . . 5741 31 lacoperator 5749 . . . 5765 17 M13 rev 5773 . . . 5789 17 LTR 6198 . . .6791 594 MMLV Psi 6854 . . . 7211 358 gag (truncated) 7276 . . . 7692417

In certain embodiments, the isolated nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:956 providedbelow:CCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGCCATGGAAACCGACACCCTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGAAATTTTATGCTGACTCAGCCCCACTCTGTGTCGGAGTCTCCGGGGAAGACGGTAACCATCTCCTGCACCCGCAGCAGTGGCAGCATTGCCAGCAACTATGTGCAGTGGTACCAGCAGCGCCCGGGCAGTGCCCCCACCACTGTGATCTATGAGGATAACCAAAGACCCTCTGGGGTCCCTGATCGGTTCTCTGGCTCCATCGACAGCTCCTCCAACTCTGCCTCCCTCACCATCTCTGGACTGAAGACTGAGGACGAGGCTGACTACTACTGTCAGTCTTATGATAGCAGCAATGTGGTATTCGGCGGAGGGACCAAGGTCACCGTCCTAGGTTCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCCGAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGAGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGTTATGAAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTTTCATACATTAGTAGTAGTGGTAGTACCATATACTACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTTTATTACTGTGCACGCTGGGACTACGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCTCCTCAGCGGCCGCACCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACAAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGAGCCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAACAGCCACTCGAGGATCCGGATTAGTCCAATTTGTTAAAGACAGGATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTACGAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCACACATGCAGCATGTATCAAAATTAATTTGGTTTTTTTTCTTAAGTATTTACATTAAATGGCCATAGTACTTAAAGTTACATTGGCTTCCTTGAAATAAACATGGAGTATTCAGAATGTGTCATAAATATTTCTAATTTTAAGATAGTATCTCCATTGGCTTTCTACTTTTTCTTTTATTTTTTTTTGTCCTCTGTCTTCCATTTGTTGTTGTTGTTGTTTGTTTGTTTGTTTGTTGGTTGGTTGGTTAATTTTTTTTTAAAGATCCTACACTATAGTTCAAGCTAGACTATTAGCTACTCTGTAACCCAGGGTGACCTTGAAGTCATGGGTAGCCTGCTGTTTTAGCCTTCCCACATCTAAGATTACAGGTATGAGCTATCATTTTTGGTATATTGATTGATTGATTGATTGATGTGTGTGTGTGTGATTGTGTTTGTGTGTGTGACTGTGAAAATGTGTGTATGGGTGTGTGTGAATGTGTGTATGTATGTGTGTGTGTGAGTGTGTGTGTGTGTGTGTGCATGTGTGTGTGTGTGACTGTGTCTATGTGTATGACTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGTGAAAAAATATTCTATGGTAGTGAGAGCCAACGCTCCGGCTCAGGTGTCAGGTTGGTTTTTGAGACAGAGTCTTTCACTTAGCTTGGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGATGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCATTGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTGCTCTTAGGAGTTTCCTAATACATCCCAAACTCAAATATATAAAGCATTTGACTTGTTCTATGCCCTAGGGGGCGGGGGGAAGCTAAGCCAGCTTTTTTTAACATTTAAAATGTTAATTCCATTTTAAATGCACAGATGTTTTTATTTCATAAGGGTTTCAATGTGCATGAATGCTGCAATATTCCTGTTACCAAAGCTAGTATAAATAAAAATAGATAAACGTGGAAATTACTTAGAGTTTCTGTCATTAACGTTTCCTTCCTCAGTTGACAACATAAATGCGCTGCTGAGCAAGCCAGTTTGCATCTGTCAGGATCAATTTCCCATTATGCCAGTCATATTAATTACTAGTCAATTAGTTGATTTTTATTTTTGACATATACATGTGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGACCACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGTGTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGACTTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGTGCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCTAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCAAGAACAACTGGACCGA [SEQ ID NO: 956]. The isolatednucleic acid molecule having the nucleotide sequence of SEQ ID NO:956encodes a FcRL-5-targeted CAR (designated as 104 FcRL5-targeted BBz CAR)comprising a fully human scFv (encoded by nucleotides 207-1010) thatcomprises a heavy chain variable region comprising amino acids havingthe sequence set forth in SEQ ID NO:216, a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:215,and a linker having an amino acid sequence of SEQ ID NO:307 positionedbetween the heavy chain variable region and the light chain variableregion, a transmembrane domain comprising a CD8 polypeptide having 137to 207 of SEQ ID NO: 960, and an intracellular domain comprising a CD3ζpolypeptide comprising amino acids 52 to 163 of SEQ ID NO: 941, and aco-stimulatory signaling region comprising a 4-1BB polypeptide havingamino acids 214-255 of SEQ ID NO: 943. Nucleotides 207-1010 of SEQ IDNO: 956 encodes the human scFv. Nucleotides 1020-1232 of SEQ ID NO: 956encodes the CD8 polypeptide comprised in the transmembrane domain.Nucleotides 1233-1358 of SEQ ID NO: 956 encodes the 4-1BB polypeptidecomprised in the intracellular domain. Nucleotides 1359-1697 of SEQ IDNO: 956 encodes the CD3zeta polypeptide comprised in the intracellulardomain. Other portions of SEQ ID NO: 956 are shown in Table 235.

TABLE 235 Nucleotide Sequence Positions of SEQ ID NO: Portions 956Number of Nucleotides antiFcRL5 scFv 104  207 . . . 1010 804 CD8a TM1020 . . . 1232 213 4-1BB 1233 . . . 1358 126 CD3zeta 1359 . . . 1697339 LTR 1977 . . . 2446 470 M13 fwd 3145 . . . 3161 17 AmpR promoter3636 . . . 3740 105 AmpR 3741 . . . 4601 861 ori 4772 . . . 5360 589 CAPbinding site 5648 . . . 5669 22 lac promoter 5684 . . . 5714 31 lacoperator 5722 . . . 5738 17 M13 rev 5746 . . . 5762 17 LTR 6171 . . .6764 594 MMLV Psi 6827 . . . 7184 358 gag (truncated) 7249 . . . 7665417

In certain embodiments, the isolated nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:957 providedbelow:CCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGCCATGGAAACCGATACACTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGCTCCTATGTGCTGACTCAGCCACCCTCAGTGTCCGTGTCCCCAGGACAGACAGCCAGCATCACCTGCTCTGGAGATAGATTGACGAATAAATATGTTTCCTGGTATCAACAGAAGCCAGGCCAGTCCCCTGTGTTGGTCATCTATGAGGATGCCAAGCGGCCCTCAGGGATCCCTGCGCGATTCTCTGGCTCCAACTCTGGGAACACAGCCACTCTGACCATCAGCGGGACCCAGGCTATGGATGAGTCTGAATATTACTGTCAGGCGTGGGACAGCAGTGTGGTGGTTTTTGGCGGAGGGACCAAGCTGACCGTCCTAGGTTCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCCGAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTTACCTTTGATGATTATGCCATGCACTGGGTCCGGCAAGCTCCAGGGAAGGGCCTGGAGTGGGTCTCAGGTATTAGTTGGAATAGTGGTAGTATAGGCTATGCGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCCCTGTATCTGCAAATGAACAGTCTGAGAGATGAGGACACGGCCTTGTATTACTGTGCAAAAGACCGAGGGGGGGGAGTTATCGTTAAGGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGCGGCCGCACCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACAAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGAGCCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAACAGCCACTCGAGGATCCGGATTAGTCCAATTTGTTAAAGACAGGATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTACGAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCACACATGCAGCATGTATCAAAATTAATTTGGTTTTTTTTCTTAAGTATTTACATTAAATGGCCATAGTACTTAAAGTTACATTGGCTTCCTTGAAATAAACATGGAGTATTCAGAATGTGTCATAAATATTTCTAATTTTAAGATAGTATCTCCATTGGCTTTCTACTTTTTCTTTTATTTTTTTTTGTCCTCTGTCTTCCATTTGTTGTTGTTGTTGTTTGTTTGTTTGTTTGTTGGTTGGTTGGTTAATTTTTTTTTAAAGATCCTACACTATAGTTCAAGCTAGACTATTAGCTACTCTGTAACCCAGGGTGACCTTGAAGTCATGGGTAGCCTGCTGTTTTAGCCTTCCCACATCTAAGATTACAGGTATGAGCTATCATTTTTGGTATATTGATTGATTGATTGATTGATGTGTGTGTGTGTGATTGTGTTTGTGTGTGTGACTGTGAAAATGTGTGTATGGGTGTGTGTGAATGTGTGTATGTATGTGTGTGTGTGAGTGTGTGTGTGTGTGTGTGCATGTGTGTGTGTGTGACTGTGTCTATGTGTATGACTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGTGAAAAAATATTCTATGGTAGTGAGAGCCAACGCTCCGGCTCAGGTGTCAGGTTGGTTTTTGAGACAGAGTCTTTCACTTAGCTTGGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGATGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCATTGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTGCTCTTAGGAGTTTCCTAATACATCCCAAACTCAAATATATAAAGCATTTGACTTGTTCTATGCCCTAGGGGGCGGGGGGAAGCTAAGCCAGCTTTTTTTAACATTTAAAATGTTAATTCCATTTTAAATGCACAGATGTTTTTATTTCATAAGGGTTTCAATGTGCATGAATGCTGCAATATTCCTGTTACCAAAGCTAGTATAAATAAAAATAGATAAACGTGGAAATTACTTAGAGTTTCTGTCATTAACGTTTCCTTCCTCAGTTGACAACATAAATGCGCTGCTGAGCAAGCCAGTTTGCATCTGTCAGGATCAATTTCCCATTATGCCAGTCATATTAATTACTAGTCAATTAGTTGATTTTTATTTTTGACATATACATGTGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGACCACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGTGTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGACTTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGTGCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCTAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCAAGAACAACTGGACCGA [SEQ ID NO: 957]. Theisolated nucleic acid molecule having the nucleotide sequence of SEQ IDNO:957 encodes a FcRL-5-targeted CAR (designated as 105 FcRL5-targetedBBz CAR) comprising a fully human scFv (encoded by nucleotides 207-1019)that comprises a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:220, a light chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:219, and a linker having an amino acid sequence of SEQ ID NO:307positioned between the heavy chain variable region and the light chainvariable region, a transmembrane domain comprising a CD8 polypeptidehaving 137 to 207 of SEQ ID NO: 960, and an intracellular domaincomprising a CD3ζ polypeptide comprising amino acids 52 to 163 of SEQ IDNO: 941, and a co-stimulatory signaling region comprising a 4-1BBpolypeptide having amino acids 214-255 of SEQ ID NO: 943. Nucleotides207-1019 of SEQ ID NO: 957 encodes the human scFv. Nucleotides 1029-1241of SEQ ID NO: 957 encodes the CD8 polypeptide comprised in thetransmembrane domain. Nucleotides 1242-1367 of SEQ ID NO: 957 encodesthe 4-1BB polypeptide comprised in the intracellular domain. Nucleotides1368-1706 of SEQ ID NO: 957 encodes the CD3zeta polypeptide comprised inthe intracellular domain. Other portions of SEQ ID NO: 957 are shown inTable 236.

TABLE 236 Nucleotide Sequence Positions of SEQ ID NO: Portions 957Number of Nucleotides antiFcRL5 scFv 105  207 . . . 1019 813 CD8a TM1029 . . . 1241 213 4-1BB 1242 . . . 1367 126 CD3zeta 1368 . . . 1706339 LTR 1986 . . . 2455 470 M13 fwd 3154 . . . 3170 17 AmpR promoter3645 . . . 3749 105 AmpR 3750 . . . 4610 861 ori 4781 . . . 5369 589 CAPbinding site 5657 . . . 5678 22 lac promoter 5693 . . . 5723 31 lacoperator 5731 . . . 5747 17 M13 rev 5755 . . . 5771 17 LTR 6180 . . .6773 594 MMLV Psi 6836 . . . 7193 358 gag (truncated) 7258 . . . 7674417

In certain embodiments, the isolated nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:958 providedbelow:CCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGCCATGGAAACCGACACCCTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGACTGCCTGTGCTGACTCAGCCACCCTCAGCGTCTGCGACCCCCGGGCAGAGGGTCACCATCTCTTGTTCTGGAACCACCTCCAACATCGGAAGTAATACTGTACACTGGTACCAGCAGCTCCCAGGGACGGCCCCCAAACTCCTCATCTATAATAATAATCAGCGGCCCTCAGGGGTCCCTGACCGATTCTCTGGCTCCAAGTCTGGCACCTCAGCCTCCCTGGCCATCAGTGGGCTCCGGTCCGAGGATGAGGCTACATATTCCTGTGCAACATGGGATGACAGCCTGAGTGGTGTGGTCTTCGGCGGAGGGACCAAGCTGACCGTCCTAGGTTCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCCGAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGTCTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGAGGGATCATCCCTATCTTTGGTACAGCAAACTACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAGATCCCGCCTACGGTGACTACGAGTATGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGCGGCCGCACCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACAAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGAGCCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAACAGCCACTCGAGGATCCGGATTAGTCCAATTTGTTAAAGACAGGATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTACGAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCACACATGCAGCATGTATCAAAATTAATTTGGTTTTTTTTCTTAAGTATTTACATTAAATGGCCATAGTACTTAAAGTTACATTGGCTTCCTTGAAATAAACATGGAGTATTCAGAATGTGTCATAAATATTTCTAATTTTAAGATAGTATCTCCATTGGCTTTCTACTTTTTCTTTTATTTTTTTTTGTCCTCTGTCTTCCATTTGTTGTTGTTGTTGTTTGTTTGTTTGTTTGTTGGTTGGTTGGTTAATTTTTTTTTAAAGATCCTACACTATAGTTCAAGCTAGACTATTAGCTACTCTGTAACCCAGGGTGACCTTGAAGTCATGGGTAGCCTGCTGTTTTAGCCTTCCCACATCTAAGATTACAGGTATGAGCTATCATTTTTGGTATATTGATTGATTGATTGATTGATGTGTGTGTGTGTGATTGTGTTTGTGTGTGTGACTGTGAAAATGTGTGTATGGGTGTGTGTGAATGTGTGTATGTATGTGTGTGTGTGAGTGTGTGTGTGTGTGTGTGCATGTGTGTGTGTGTGACTGTGTCTATGTGTATGACTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGTGAAAAAATATTCTATGGTAGTGAGAGCCAACGCTCCGGCTCAGGTGTCAGGTTGGTTTTTGAGACAGAGTCTTTCACTTAGCTTGGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGATGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCATTGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTGCTCTTAGGAGTTTCCTAATACATCCCAAACTCAAATATATAAAGCATTTGACTTGTTCTATGCCCTAGGGGGCGGGGGGAAGCTAAGCCAGCTTTTTTTAACATTTAAAATGTTAATTCCATTTTAAATGCACAGATGTTTTTATTTCATAAGGGTTTCAATGTGCATGAATGCTGCAATATTCCTGTTACCAAAGCTAGTATAAATAAAAATAGATAAACGTGGAAATTACTTAGAGTTTCTGTCATTAACGTTTCCTTCCTCAGTTGACAACATAAATGCGCTGCTGAGCAAGCCAGTTTGCATCTGTCAGGATCAATTTCCCATTATGCCAGTCATATTAATTACTAGTCAATTAGTTGATTTTTATTTTTGACATATACATGTGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGACCACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGTGTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGACTTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGTGCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCTAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCAAGAACAACTGGACCGA [SEQ ID NO:958]. The isolated nucleic acid molecule having the nucleotide sequenceof SEQ ID NO:958 encodes a FcRL-5-targeted CAR (designated as 109FcRL5-targeted BBz CAR) comprising a fully human scFv (encoded bynucleotides 207-1031) that comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:236, alight chain variable region comprising amino acids having the sequenceset forth in SEQ ID NO:235, and a linker having an amino acid sequenceof SEQ ID NO:307 positioned between the heavy chain variable region andthe light chain variable region, a transmembrane domain comprising a CD8polypeptide having 137 to 207 of SEQ ID NO: 960, and an intracellulardomain comprising a CD3ζ polypeptide comprising amino acids 52 to 163 ofSEQ ID NO: 941, and a co-stimulatory signaling region comprising a 4-1BBpolypeptide having amino acids 214-255 of SEQ ID NO: 943. Nucleotides207-1031 of SEQ ID NO: 957 encodes the human scFv. Nucleotides 1041-1253of SEQ ID NO: 958 encodes the CD8 polypeptide comprised in thetransmembrane domain. Nucleotides 1254-1379 of SEQ ID NO: 958 encodesthe 4-1BB polypeptide comprised in the intracellular domain. Nucleotides1380-1718 of SEQ ID NO: 958 encodes the CD3zeta polypeptide comprised inthe intracellular domain. Other portions of SEQ ID NO: 958 are shown inTable 237.

TABLE 237 Nucleotide Sequence Positions of SEQ ID Portions NO: 958Number of Nucleotides anti-FcRL5 scFv 109  207 . . . 1031 825 CD8a TM1041 . . . 1253 213 4-1BB 1254 . . . 1379 126 CD3zeta 1380 . . . 1718339 LTR 1998 . . . 2467 470 M13 fwd 3166 . . . 3182 17 AmpR promoter3657 . . . 3761 105 AmpR 3762 . . . 4622 861 ori 4793 . . . 5381 589 CAPbinding site 5669 . . . 5690 22 lac promoter 5705 . . . 5735 31 lacoperator 5743 . . . 5759 17 M13 rev 5767 . . . 5783 17 LTR 6192 . . .6785 594 MMLV Psi 6848 . . . 7205 358 gag (truncated) 7270 . . . 7686417

In certain embodiments, the isolated nucleic acid molecule comprisesnucleic acids having the sequence set forth in SEQ ID NO:959 providedbelow:CCGGTGGTACCTCACCCTTACCGAGTCGGCGACACAGTGTGGGTCCGCCGACACCAGACTAAGAACCTAGAACCTCGCTGGAAAGGACCTTACACAGTCCTGCTGACCACCCCCACCGCCCTCAAAGTAGACGGCATCGCAGCTTGGATACACGCCGCCCACGTGAAGGCTGCCGACCCCGGGGGTGGACCATCCTCTAGACTGCCATGGAAACCGATACACTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGATCCACAGGCGATGTTGTGATGACTCAGTCTCCACCCTCCCTGTCCGTCACCCCTGGAGAGCCGGCCTCCATCACCTGCAGGTCTAGTCAGAGCCTCCTGGAAAGAAATGCATACAACTACTTGGATTGGTACCTGCAGAGGCCAGGACAGTCTCCACAGCTCCTGATCTACTTGGGTTCTAATCGGGCCGCCGGGGTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCAGAGATTTTACACTGAAAATCAGCAGAGTGGAGCCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCTACAAGCTCCGTTCACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTTCTAGAGGTGGTGGTGGTAGCGGCGGCGGCGGCTCTGGTGGTGGTGGATCCCTCGAGATGGCCGAAGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACTACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAATGGGGCCCGTTTCAGGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTCACCGTCTCTTCAGCGGCCGCACCCACCACGACGCCAGCGCCGCGACCACCAACCCCGGCGCCCACGATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCCTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACAAACGGGGCAGAAAGAAGCTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGAGCCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCTAACAGCCACTCGAGGATCCGGATTAGTCCAATTTGTTAAAGACAGGATATCAGTGGTCCAGGCTCTAGTTTTGACTCAACAATATCACCAGCTGAAGCCTATAGAGTACGAGCCATAGATAAAATAAAAGATTTTATTTAGTCTCCAGAAAAAGGGGGGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAGAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCACACATGCAGCATGTATCAAAATTAATTTGGTTTTTTTTCTTAAGTATTTACATTAAATGGCCATAGTACTTAAAGTTACATTGGCTTCCTTGAAATAAACATGGAGTATTCAGAATGTGTCATAAATATTTCTAATTTTAAGATAGTATCTCCATTGGCTTTCTACTTTTTCTTTTATTTTTTTTTGTCCTCTGTCTTCCATTTGTTGTTGTTGTTGTTTGTTTGTTTGTTTGTTGGTTGGTTGGTTAATTTTTTTTTAAAGATCCTACACTATAGTTCAAGCTAGACTATTAGCTACTCTGTAACCCAGGGTGACCTTGAAGTCATGGGTAGCCTGCTGTTTTAGCCTTCCCACATCTAAGATTACAGGTATGAGCTATCATTTTTGGTATATTGATTGATTGATTGATTGATGTGTGTGTGTGTGATTGTGTTTGTGTGTGTGACTGTGAAAATGTGTGTATGGGTGTGTGTGAATGTGTGTATGTATGTGTGTGTGTGAGTGTGTGTGTGTGTGTGTGCATGTGTGTGTGTGTGACTGTGTCTATGTGTATGACTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTTGTGAAAAAATATTCTATGGTAGTGAGAGCCAACGCTCCGGCTCAGGTGTCAGGTTGGTTTTTGAGACAGAGTCTTTCACTTAGCTTGGAATTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGCGCCTGATGCGGTATTTTCTCCTTACGCATCTGTGCGGTATTTCACACCGCATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCCAGCCCCGACACCCGCCAACACCCGCTGACGCGCCCTGACGGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCATGTGTCAGAGGTTTTCACCGTCATCACCGAAACGCGCGATGACGAAAGGGCCTCGTGATACGCCTATTTTTATAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCATTGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCTTTGCTCTTAGGAGTTTCCTAATACATCCCAAACTCAAATATATAAAGCATTTGACTTGTTCTATGCCCTAGGGGGCGGGGGGAAGCTAAGCCAGCTTTTTTTAACATTTAAAATGTTAATTCCATTTTAAATGCACAGATGTTTTTATTTCATAAGGGTTTCAATGTGCATGAATGCTGCAATATTCCTGTTACCAAAGCTAGTATAAATAAAAATAGATAAACGTGGAAATTACTTAGAGTTTCTGTCATTAACGTTTCCTTCCTCAGTTGACAACATAAATGCGCTGCTGAGCAAGCCAGTTTGCATCTGTCAGGATCAATTTCCCATTATGCCAGTCATATTAATTACTAGTCAATTAGTTGATTTTTATTTTTGACATATACATGTGAATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAAATACATAACTGAGAATAGAAAAGTTCAGATCAAGGTCAGGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGAACAGCTGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCAGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTATGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGGGCGCCAGTCCTCCGATTGACTGAGTCGCCCGGGTACCCGTGTATCCAATAAACCCTCTTGCAGTTGCATCCGACTTGTGGTCTCGCTGTTCCTTGGGAGGGTCTCCTCTGAGTGATTGACTACCCGTCAGCGGGGGTCTTTCATTTGGGGGCTCGTCCGGGATCGGGAGACCCCTGCCCAGGGACCACCGACCCACCACCGGGAGGTAAGCTGGCCAGCAACTTATCTGTGTCTGTCCGATTGTCTAGTGTCTATGACTGATTTTATGCGCCTGCGTCGGTACTAGTTAGCTAACTAGCTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCGGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGACTTCGGGGGCCGTTTTTGTGGCCCGACCTGAGTCCTAAAATCCCGATCGTTTAGGACTCTTTGGTGCACCCCCCTTAGAGGAGGGATATGTGGTTCTGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGGACCGAAGCCGCGCCGCGCGTCTTGTCTGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATATGGGCCCGGGCTAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGTCGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGAGACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGACCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTAAGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCCCTTTATCCAGCCCTCACTCCTTCTCTAGGCGCCCCCATATGGCCATATGAGATCTTATATGGGGCACCCCCGCCCCTTGTAAACTTCCCTGACCCTGACATGACAAGAGTTACTAACAGCCCCTCTCTCCAAGCTCACTTACAGGCTCTCTACTTAGTCCAGCACGAAGTCTGGAGACCTCTGGCGGCAGCCTACCAAGAACAACTGGACCGA [SEQ ID NO: 959]. Theisolated nucleic acid molecule having the nucleotide sequence of SEQ IDNO:959 encodes a FcRL-5-targeted CAR (designated as 117 FcRL5-targetedBBz CAR) comprising a fully human scFv (encoded by nucleotides 207-1025of SEQ ID NO:959) that comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:268, alight chain variable region comprising amino acids having the sequenceset forth in SEQ ID NO:267, and a linker having an amino acid sequenceof SEQ ID NO:307 positioned between the heavy chain variable region andthe light chain variable region, a transmembrane domain comprising a CD8polypeptide having 137 to 207 of SEQ ID NO: 960, and an intracellulardomain comprising a CD3ζ polypeptide comprising amino acids 52 to 163 ofSEQ ID NO: 941, and a co-stimulatory signaling region comprising a 4-1BBpolypeptide having amino acids 214-255 of SEQ ID NO: 943. Nucleotides207-1025 of SEQ ID NO: 959 encodes the human scFv. Nucleotides 1035-1247of SEQ ID NO: 959 encodes the CD8 polypeptide comprised in thetransmembrane domain. Nucleotides 1248-1373 of SEQ ID NO: 959 encodesthe 4-1BB polypeptide comprised in the intracellular domain. Nucleotides1374-1712 of SEQ ID NO: 959 encodes the CD3zeta polypeptide comprised inthe intracellular domain. Other portions of SEQ ID NO: 959 are shown inTable 238.

TABLE 238 Nucleotide Sequence Positions of SEQ ID Portions NO: 959Number of Nucleotides anti-FcRL5 scFv 117  207 . . . 1025 819 CD8a TM1035 . . . 1247 213 4-1BB 1248 . . . 1373 126 CD3zeta 1374 . . . 1712339 LTR 1992 . . . 2461 470 M13 fwd 3160 . . . 3176 17 AmpR promoter3651 . . . 3755 105 AmpR 3756 . . . 4616 861 ori 4787 . . . 5375 589 CAPbinding site 5663 . . . 5684 22 lac promoter 5699 . . . 5729 31 lacoperator 5737 . . . 5753 17 M13 rev 5761 . . . 5777 17 LTR 6186 . . .6779 594 MMLV Psi 6842 . . . 7199 358 gag (truncated) 7264 . . . 7680417

In certain embodiments, the isolated nucleic acid molecule encodes afunctional portion of a presently disclosed FcRL5-targeted CAR. As usedherein, the term “functional portion” refers to any portion, part orfragment of a presently disclosed FcRL5-targeted CAR, which portion,part or fragment retains the biological activity of the FcRL5-targetedCAR (the parent CAR). For example, functional portions encompass theportions, parts or fragments of a presently disclosed FcRL5-targeted CARthat retains the ability to recognize a target cell, to treat a disease,e.g., multiple myeloma, to a similar, same, or even a higher extent asthe parent CAR. In certain embodiments, an isolated nucleic acidmolecule encoding a functional portion of a presently disclosedFcRL5-targeted CAR can encode a protein comprising, e.g., about 10%,20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, and 95%, or more of the parent CAR, e.g., of the nucleic acidsequences set forth in SEQ ID NO:951, SEQ ID NO:952, SEQ ID NO:953, SEQID NO:954, SEQ ID NO:955, SEQ ID NO:956, SEQ ID NO:957, SEQ ID NO:958 orSEQ ID NO:959.

III. Immunoresponsive Cells

The presently disclosed subject matter provides immunoresponsive cellsexpressing a CAR that comprises an extracellular antigen-binding domain,a transmembrane domain and an intracellular domain, where theextracellular antigen-binding domain specifically binds to FcRL5 (e.g.,human FcRL5), as described above. In certain embodiments, theextracellular antigen-binding domain specifically binds to domain 7 ofFcRL5. In certain embodiments, the extracellular antigen-binding domainspecifically binds to domain 8 of FcRL5. In certain embodiments, theextracellular antigen-binding domain specifically binds to domain 9 ofFcRL5. The immunoresponsive cells can be transduced with a presentlydisclosed CAR such that the cells express the CAR. The presentlydisclosed subject matter also provides methods of using such cells forthe treatment of a tumor, e.g., multiple myeloma (MM). Theimmunoresponsive cells of the presently disclosed subject matter can becells of the lymphoid lineage. The lymphoid lineage, comprising B, T andnatural killer (NK) cells, provides for the production of antibodies,regulation of the cellular immune system, detection of foreign agents inthe blood, detection of cells foreign to the host, and the like.Non-limiting examples of immunoresponsive cells of the lymphoid lineageinclude T cells, Natural Killer (NK) cells, cytotoxic T lymphocytes(CTLs), regulatory T cells, embryonic stem cells, and pluripotent stemcells (e.g., those from which lymphoid cells may be differentiated). Tcells can be lymphocytes that mature in the thymus and are chieflyresponsible for cell-mediated immunity. T cells are involved in theadaptive immune system. The T cells of the presently disclosed subjectmatter can be any type of T cells, including, but not limited to, Thelper cells, cytotoxic T cells, memory T cells (including centralmemory T cells, stem-cell-like memory T cells (or stem-like memory Tcells), and two types of effector memory T cells: e.g., T_(EM) cells andT_(EMRA) cells), Regulatory T cells (also known as suppressor T cells),Natural killer T cells, Mucosal associated invariant T cells, and γδ Tcells. In certain embodiments, the CAR-expressing T cells express Foxp3to achieve and maintain a T regulatory phenotype. Natural killer (NK)cells can be lymphocytes that are part of cell-mediated immunity and actduring the innate immune response. NK cells do not require prioractivation in order to perform their cytotoxic effect on target cells.Cytotoxic T cells (CTL or killer T cells) are a subset of T lymphocytescapable of inducing the death of infected somatic or tumor cells.

The immunoresponsive cells of the presently disclosed subject matter canexpress an extracellular antigen-binding domain (e.g., an scFV, a Fabthat is optionally crosslinked, or a F(ab)₂) that specifically binds toFcRL5 (e.g., human FcRL5), for the treatment of multiple myeloma. Suchimmunoresponsive cells can be administered to a subject (e.g., a humansubject) in need thereof for the treatment of multiple myeloma. Incertain embodiments, the immunoresponsive cell is a T cell. The T cellcan be a CD4⁺ T cell or a CD8⁺ T cell. In certain embodiments, the Tcell is a CD4⁺ T cell. In another embodiment, the T cell is a CD8⁺ Tcell.

A presently disclosed immunoresponsive cell can be further transducedwith at least one co-stimulatory ligand, such that the immunoresponsivecell co-expresses or is induced to co-express the FcRL5-specific CAR andthe at least one co-stimulatory ligand. The interaction between theFcRL5-specific CAR and at least one co-stimulatory ligand provides anon-antigen-specific signal important for full activation of animmunoresponsive cell (e.g., T cell). Co-stimulatory ligands include,but are not limited to, members of the tumor necrosis factor (TNF)superfamily, and immunoglobulin (Ig) superfamily ligands. TNF is acytokine involved in systemic inflammation and stimulates the acutephase reaction. Its primary role is in the regulation of immune cells.Members of TNF superfamily share a number of common features. Themajority of TNF superfamily members are synthesized as type IItransmembrane proteins (extracellular C-terminus) containing a shortcytoplasmic segment and a relatively long extracellular region. TNFsuperfamily members include, without limitation, nerve growth factor(NGF), CD40L (CD40L)/CD154, CD137L/4-1BBL, TNF-α, CD134L/OX40L/CD252,CD27L/CD70, Fas ligand (FasL), CD30L/CD153, tumor necrosis factor beta(TNFβ)/lymphotoxin-alpha (LTα), lymphotoxin-beta (LTβ), CD257/Bcell-activating factor (BAFF)/Blys/THANK/Tall-1, glucocorticoid-inducedTNF Receptor ligand (GITRL), and TNF-related apoptosis-inducing ligand(TRAIL), LIGHT (TNFSF14). The immunoglobulin (Ig) superfamily is a largegroup of cell surface and soluble proteins that are involved in therecognition, binding, or adhesion processes of cells. These proteinsshare structural features with immunoglobulins—they possess animmunoglobulin domain (fold). Immunoglobulin superfamily ligandsinclude, but are not limited to, CD80 and CD86, both ligands for CD28,PD-L1/(B7-H1) that ligands for PD-1. In certain embodiments, the atleast one co-stimulatory ligand is selected from the group consisting of4-1BBL, CD80, CD86, CD70, OX40L, CD48, TNFRSF14, PD-L1, and combinationsthereof. In certain embodiments, the immunoresponsive cell is transducedwith one co-stimulatory ligand that is 4-1BBL. In certain embodiments,the immunoresponsive cell is transduced with two co-stimulatory ligandsthat are 4-1BBL and CD80. CARs transduced with at least oneco-stimulatory ligand are described in U.S. Pat. No. 8,389,282, which isincorporated by reference in its entirety.

Furthermore, a presently disclosed immunoresponsive cell can be furthertransduced with at least one cytokine, such that the immunoresponsivecell secretes the at least one cytokine as well as expresses theFcRL5-specific CAR. In certain embodiments, the at least one cytokine isselected from the group consisting of IL-2, IL-3, IL-6, IL-7, IL-11,IL-12, IL-15, IL-17, and IL-21. In certain embodiments, the cytokine isIL-12.

The FcRL5-specific or FcRL5-targeted human lymphocytes that can be usedin peripheral donor lymphocytes, e.g., those disclosed in Sadelain, M.,et al. 2003 Nat Rev Cancer 3:35-45 (disclosing peripheral donorlymphocytes genetically modified to express CARs), in Morgan, R. A., etal. 2006 Science 314:126-129 (disclosing peripheral donor lymphocytesgenetically modified to express a full-length tumor antigen-recognizingT cell receptor complex comprising the α and β heterodimer), in Panelli,M. C., et al. 2000 J Immunol 164:495-504; Panelli, M. C., et al. 2000 JImmunol 164:4382-4392 (disclosing lymphocyte cultures derived from tumorinfiltrating lymphocytes (TILs) in tumor biopsies), and in Dupont, J.,et al. 2005 Cancer Res 65:5417-5427; Papanicolaou, G. A., et al. 2003Blood 102:2498-2505 (disclosing selectively in vitro-expandedantigen-specific peripheral blood leukocytes employing artificialantigen-presenting cells (AAPCs) or pulsed dendritic cells). Theimmunoresponsive cells (e.g., T cells) can be autologous, non-autologous(e.g., allogeneic), or derived in vitro from engineered progenitor orstem cells.

In certain embodiments, a presently disclosed immunoresponsive cell(e.g., T cell) expresses from about 1 to about 4, from about 2 to about4, from about 3 to about 4, from about 1 to about 2, from about 1 toabout 3, or from about 2 to about 3 vector copy numbers/cell of apresently disclosed FcRL5-specific CAR.

The unpurified source of CTLs may be any known in the art, such as thebone marrow, fetal, neonate or adult or other hematopoietic cell source,e.g., fetal liver, peripheral blood or umbilical cord blood. Varioustechniques can be employed to separate the cells. For instance, negativeselection methods can remove non-CTLs initially. Monoclonal antibodiesare particularly useful for identifying markers associated withparticular cell lineages and/or stages of differentiation for bothpositive and negative selections.

A large proportion of terminally differentiated cells can be initiallyremoved by a relatively crude separation. For example, magnetic beadseparations can be used initially to remove large numbers of irrelevantcells. Preferably, at least about 80%, usually at least 70% of the totalhematopoietic cells will be removed prior to cell isolation.

Procedures for separation include, but are not limited to, densitygradient centrifugation; resetting; coupling to particles that modifycell density; magnetic separation with antibody-coated magnetic beads;affinity chromatography; cytotoxic agents joined to or used inconjunction with a mAb, including, but not limited to, complement andcytotoxins; and panning with antibody attached to a solid matrix, e.g.plate, chip, elutriation or any other convenient technique.

Techniques for separation and analysis include, but are not limited to,flow cytometry, which can have varying degrees of sophistication, e.g.,a plurality of color channels, low angle and obtuse light scatteringdetecting channels, impedance channels. The cells can be selectedagainst dead cells, by employing dyes associated with dead cells such aspropidium iodide (PI). Preferably, the cells are collected in a mediumcomprising 2% fetal calf serum (FCS) or 0.2% bovine serum albumin (BSA)or any other suitable, preferably sterile, isotonic medium.

IV. Vectors

Genetic modification of immunoresponsive cells (e.g., T cells, CTLcells, NK cells) can be accomplished by transducing a substantiallyhomogeneous cell composition with a recombinant DNA or RNA construct.The vector can be a retroviral vector (e.g., gamma retroviral), which isemployed for the introduction of the DNA or RNA construct into the hostcell genome. For example, a polynucleotide encoding the FcRL5-specificCAR can be cloned into a retroviral vector and expression can be drivenfrom its endogenous promoter, from the retroviral long terminal repeat,or from an alternative internal promoter.

Non-viral vectors or RNA may be used as well. Random chromosomalintegration, or targeted integration (e.g., using a nuclease,transcription activator-like effector nucleases (TALENs), Zinc-fingernucleases (ZFNs), and/or clustered regularly interspaced shortpalindromic repeats (CRISPRs), or transgene expression (e.g., using anatural or chemically modified RNA) can be used.

For initial genetic modification of the cells to provide FcRL5-specificCAR expressing cells, a retroviral vector is generally employed fortransduction, however any other suitable viral vector or non-viraldelivery system can be used. For subsequent genetic modification of thecells to provide cells comprising an antigen presenting complexcomprising at least two co-stimulatory ligands, retroviral gene transfer(transduction) likewise proves effective. Combinations of retroviralvector and an appropriate packaging line are also suitable, where thecapsid proteins will be functional for infecting human cells. Variousamphotropic virus-producing cell lines are known, including, but notlimited to, PA12 (Miller, et al. (1985) Mol. Cell. Biol. 5:431-437);PA317 (Miller, et al. (1986) Mol. Cell. Biol. 6:2895-2902); and CRIP(Danos, et al. (1988) Proc. Natl. Acad. Sci. USA 85:6460-6464).Non-amphotropic particles are suitable too, e.g., particles pseudotypedwith VSVG, RD114 or GALV envelope and any other known in the art.

Possible methods of transduction also include direct co-culture of thecells with producer cells, e.g., by the method of Bregni, et al. (1992)Blood 80:1418-1422, or culturing with viral supernatant alone orconcentrated vector stocks with or without appropriate growth factorsand polycations, e.g., by the method of Xu, et al. (1994) Exp. Hemat.22:223-230; and Hughes, et al. (1992) J Clin. Invest. 89:1817.

Transducing viral vectors can be used to express a co-stimulatory ligand(e.g., 4-1BBL and IL-12) in an immunoresponsive cell. Preferably, thechosen vector exhibits high efficiency of infection and stableintegration and expression (see, e.g., Cayouette et al., Human GeneTherapy 8:423-430, 1997; Kido et al., Current Eye Research 15:833-844,1996; Bloomer et al., Journal of Virology 71:6641-6649, 1997; Naldini etal., Science 272:263 267, 1996; and Miyoshi et al., Proc. Natl. Acad.Sci. U.S.A. 94:10319, 1997). Other viral vectors that can be usedinclude, for example, adenoviral, lentiviral, and adeno-associated viralvectors, vaccinia virus, a bovine papilloma virus, or a herpes virus,such as Epstein-Barr Virus (also see, for example, the vectors ofMiller, Human Gene Therapy 15-14, 1990; Friedman, Science 244:1275-1281,1989; Eglitis et al., BioTechniques 6:608-614, 1988; Tolstoshev et al.,Current Opinion in Biotechnology 1:55-61, 1990; Sharp, The Lancet337:1277-1278, 1991; Cornetta et al., Nucleic Acid Research andMolecular Biology 36:311-322, 1987; Anderson, Science 226:401-409, 1984;Moen, Blood Cells 17:407-416, 1991; Miller et al., Biotechnology7:980-990, 1989; Le Gal La Salle et al., Science 259:988-990, 1993; andJohnson, Chest 107:77S-83S, 1995). Retroviral vectors are particularlywell developed and have been used in clinical settings (Rosenberg etal., N. Engl. J. Med 323:370, 1990; Anderson et al., U.S. Pat. No.5,399,346).

In certain non-limiting embodiments, the vector expressing a presentlydisclosed FcRL5-targeted CAR is a retroviral vector, e.g., a 293galv9retroviral vector.

Non-viral approaches can also be employed for the expression of aprotein in cell. For example, a nucleic acid molecule can be introducedinto a cell by administering the nucleic acid in the presence oflipofection (Feigner et al., Proc. Nat'l. Acad. Sci. U.S.A. 84:7413,1987; Ono et al., Neuroscience Letters 17:259, 1990; Brigham et al., Am.J. Med. Sci. 298:278, 1989; Staubinger et al., Methods in Enzymology101:512, 1983), asialoorosomucoid-polylysine conjugation (Wu et al.,Journal of Biological Chemistry 263:14621, 1988; Wu et al., Journal ofBiological Chemistry 264:16985, 1989), or by micro-injection undersurgical conditions (Wolff et al., Science 247:1465, 1990). Othernon-viral means for gene transfer include transfection in vitro usingcalcium phosphate, DEAE dextran, electroporation, and protoplast fusion.Liposomes can also be potentially beneficial for delivery of DNA into acell. Transplantation of normal genes into the affected tissues of asubject can also be accomplished by transferring a normal nucleic acidinto a cultivatable cell type ex vivo (e.g., an autologous orheterologous primary cell or progeny thereof), after which the cell (orits descendants) are injected into a targeted tissue or are injectedsystemically. Recombinant receptors can also be derived or obtainedusing transposases or targeted nucleases (e.g. Zinc finger nucleases,meganucleases, or TALE nucleases). Transient expression may be obtainedby RNA electroporation.

cDNA expression for use in polynucleotide therapy methods can bedirected from any suitable promoter (e.g., the human cytomegalovirus(CMV), simian virus 40 (SV40), or metallothionein promoters), andregulated by any appropriate mammalian regulatory element or intron(e.g. the elongation factor 1 α enhancer/promoter/intron structure). Forexample, if desired, enhancers known to preferentially direct geneexpression in specific cell types can be used to direct the expressionof a nucleic acid. The enhancers used can include, without limitation,those that are characterized as tissue- or cell-specific enhancers.Alternatively, if a genomic clone is used as a therapeutic construct,regulation can be mediated by the cognate regulatory sequences or, ifdesired, by regulatory sequences derived from a heterologous source,including any of the promoters or regulatory elements described above.

The resulting cells can be grown under conditions similar to those forunmodified cells, whereby the modified cells can be expanded and usedfor a variety of purposes.

V. Polypeptides and Analogs and Polynucleotides

Also included in the presently disclosed subject matter areextracellular antigen-binding domains that specifically binds to FcRL5(e.g., human FcRL5) (e.g., an scFv, such as an scFv derived fromantibodies F56 and F119, a Fab, or a (Fab)₂), CD3ζ, CD8, CD28, etc.polypeptides or fragments thereof, and polynucleotides encoding thereofthat are modified in ways that enhance their anti-tumor activity whenexpressed in an immunoresponsive cell. In certain embodiments, thepresently disclosed subject matter further provides extracellularantigen-binding domains that specifically binds to domain 9 FcRL5 (e.g.,domain 7, domain 8 or domain 9 of human FcRL5) (e.g., an scFv, a Fab, ora (Fab)₂), CD3ζ, CD8, CD28, etc. polypeptides or fragments thereof, andpolynucleotides encoding thereof that are modified in ways that enhancetheir anti-tumor activity when expressed in an immunoresponsive cell.

The presently disclosed subject matter provides methods for optimizingan amino acid sequence or a nucleic acid sequence by producing analteration in the sequence. Such alterations may comprise certainmutations, deletions, insertions, or post-translational modifications.The presently disclosed subject matter further comprises analogs of anynaturally-occurring polypeptide of the presently disclosed subjectmatter. Analogs can differ from a naturally-occurring polypeptide of thepresently disclosed subject matter by amino acid sequence differences,by post-translational modifications, or by both. Analogs of thepresently disclosed subject matter can generally exhibit at least about85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%,about 96%, about 97%, about 98%, about 99% or more identity with all orpart of a naturally-occurring amino, acid sequence of the presentlydisclosed subject matter. The length of sequence comparison is at least5, 10, 15, 20, 25, 50, 75, 100 or more amino acid residues. Again, in anexemplary approach to determining the degree of identity, a BLASTprogram may be used, with a probability score between e⁻³ and e⁻¹⁰⁰indicating a closely related sequence. Modifications comprise in vivoand in vitro chemical derivatization of polypeptides, e.g., acetylation,carboxylation, phosphorylation, or glycosylation; such modifications mayoccur during polypeptide synthesis or processing or following treatmentwith isolated modifying enzymes. Analogs can also differ from thenaturally-occurring polypeptides of the presently disclosed subjectmatter by alterations in primary sequence. These include geneticvariants, both natural and induced (for example, resulting from randommutagenesis by irradiation or exposure to ethanemethylsulfate or bysite-specific mutagenesis as described in Sambrook, Fritsch andManiatis, Molecular Cloning: A Laboratory Manual (2d ed.), CSH Press,1989, or Ausubel et al., supra). Also included are cyclized peptides,molecules, and analogs which contain residues other than L-amina acids,e.g., D-amino acids or non-naturally occurring or synthetic amino acids,e.g., beta (β) or gamma (γ) amino acids.

In addition to full-length polypeptides, the presently disclosed subjectmatter also provides fragments of any one of the polypeptides or peptidedomains of the presently disclosed subject matter. A fragment can be atleast 5, 10, 13, or 15 amino acids. In certain embodiments, a fragmentis at least 20 contiguous amino acids, at least 30 contiguous aminoacids, or at least 50 contiguous amino acids. In certain embodiments, afragment is at least 60 to 80, 100, 200, 300 or more contiguous aminoacids. Fragments of the presently disclosed subject matter can begenerated by methods known to those of ordinary skill in the art or mayresult from normal protein processing (e.g., removal of amino acids fromthe nascent polypeptide that are not required for biological activity orremoval of amino acids by alternative mRNA splicing or alternativeprotein processing events).

Non-protein analogs have a chemical structure designed to mimic thefunctional activity of a protein of the invention. Such analogs areadministered according to methods of the presently disclosed subjectmatter. Such analogs may exceed the physiological activity of theoriginal polypeptide. Methods of analog design are well known in theart, and synthesis of analogs can be carried out according to suchmethods by modifying the chemical structures such that the resultantanalogs increase the anti-neoplastic activity of the originalpolypeptide when expressed in an immunoresponsive cell. These chemicalmodifications include, but are not limited to, substituting alternativeR groups and varying the degree of saturation at specific carbon atomsof a reference polypeptide. The protein analogs can be relativelyresistant to in vivo degradation, resulting in a more prolongedtherapeutic effect upon administration. Assays for measuring functionalactivity include, but are not limited to, those described in theExamples below.

In accordance with the presently disclosed subject matter, thepolynucleotides encoding an extracellular antigen-binding domain thatspecifically binds to FcRL5 (e.g., an scFV (e.g., an scFv derived fromantibodies F56 and F119), a Fab, Fab′ or a (Fab′)₂), CD3ζ, CD8, CD28)can be modified by codon optimization. Codon optimization can alter bothnaturally occurring and recombinant gene sequences to achieve thehighest possible levels of productivity in any given expression system.Factors that are involved in different stages of protein expressioninclude codon adaptability, mRNA structure, and various cis-elements intranscription and translation. Any suitable codon optimization methodsor technologies that are known to ones skilled in the art can be used tomodify the polynucleotids of the presently disclosed subject matter,including, but not limited to, OPTIMUMGENE™, Encor optimization, andBlue Heron.

VI. Administration

FcRL5-specific CARs and immunoresponsive cells expressing thereof of thepresently disclosed subject matter can be provided systemically ordirectly to a subject for treating or preventing a neoplasia. In certainembodiments, the FcRL5-specific CARs and immunoresponsive cellsexpressing thereof are directly injected into an organ of interest(e.g., an organ affected by a neoplasia). Alternatively or additionally,the FcRL5-specific CARs and immunoresponsive cells expressing thereofare provided indirectly to the organ of interest, for example, byadministration into the circulatory system (e.g., the tumorvasculature). Expansion and differentiation agents can be provided priorto, during or after administration of cells and compositions to increaseproduction of T cells in vitro or in vivo.

FcRL5-specific CARs and immunoresponsive cells expressing thereof of thepresently disclosed subject matter can be administered in anyphysiologically acceptable vehicle, normally intravascularly, althoughthey may also be introduced into bone or other convenient site where thecells may find an appropriate site for regeneration and differentiation(e.g., thymus). Usually, at least 1×10⁵ cells can be administered,eventually reaching 1×10¹⁰ or more. A cell population comprisingimmunoresponsive cells expressing a FcRL5-specific CAR can comprise apurified population of cells. Those skilled in the art can readilydetermine the percentage of immunoresponsive cells in a cell populationusing various well-known methods, such as fluorescence activated cellsorting (FACS). The ranges of purity in cell populations comprisinggenetically modified immunoresponsive cells expressing a FcRL5-specificCAR can be from about 50% to about 55%, from about 55% to about 60%,from about 65% to about 70%, from about 70% to about 75%, from about 75%to about 80%, from about 80% to about 85%; from about 85% to about 90%,from about 90% to about 95%, or from about 95 to about 100%. Dosages canbe readily adjusted by those skilled in the art (e.g., a decrease inpurity may require an increase in dosage). The immunoresponsive cellscan be introduced by injection, catheter, or the like. If desired,factors can also be included, including, but not limited to,interleukins, e.g. IL-2, IL-3, IL 6, IL-11, IL-7, IL-12, IL-15, IL-21,as well as the other interleukins, the colony stimulating factors, suchas G-, M- and GM-CSF, interferons, e.g., γ-interferon.

Compositions of the presently disclosed subject matter comprisepharmaceutical compositions comprising immunoresponsive cells expressinga FcRL5-specific CAR and a pharmaceutically acceptable carrier.Administration can be autologous or non-autologous. For example,immunoresponsive cells expressing a FcRL5-specific CAR and compositionscomprising thereof can be obtained from one subject, and administered tothe same subject or a different, compatible subject. Peripheral bloodderived T cells of the presently disclosed subject matter or theirprogeny (e.g., in vivo, ex vivo or in vitro derived) can be administeredvia localized injection, including catheter administration, systemicinjection, localized injection, intravenous injection, or parenteraladministration. When administering a pharmaceutical composition of thepresently disclosed subject matter (e.g., a pharmaceutical compositioncomprising immunoresponsive cells expressing a FcRL5-specific CAR), itcan be formulated in a unit dosage injectable form (solution,suspension, emulsion).

VII. Formulations

Immunoresponsive cells expressing a generally FcRL5-specific CAR andcompositions comprising thereof of the presently disclosed subjectmatter can be conveniently provided as sterile liquid preparations,e.g., isotonic aqueous solutions, suspensions, emulsions, dispersions,or viscous compositions, which may be buffered to a selected pH. Liquidpreparations are normally easier to prepare than gels, other viscouscompositions, and solid compositions. Additionally, liquid compositionsare somewhat more convenient to administer, especially by injection.Viscous compositions, on the other hand, can be formulated within theappropriate viscosity range to provide longer contact periods withspecific tissues. Liquid or viscous compositions can comprise carriers,which can be a solvent or dispersing medium containing, for example,water, saline, phosphate buffered saline, polyol (for example, glycerol,propylene glycol, liquid polyethylene glycol, and the like) and suitablemixtures thereof.

Sterile injectable solutions can be prepared by incorporating thecompositions comprising immunoresponsive cells expressing a generallyFcRL5-specific CAR of the presently disclosed subject matter in therequired amount of the appropriate solvent with various amounts of theother ingredients, as desired. Such compositions may be in admixturewith a suitable carrier, diluent, or excipient such as sterile water,physiological saline, glucose, dextrose, or the like. The compositionscan also be lyophilized. The compositions can contain auxiliarysubstances such as wetting, dispersing, or emulsifying agents (e.g.,methylcellulose), pH buffering agents, gelling or viscosity enhancingadditives, preservatives, flavoring agents, colors, and the like,depending upon the route of administration and the preparation desired.Standard texts, such as “REMINGTON'S PHARMACEUTICAL SCIENCE,” 17thedition, 1985, incorporated herein by reference, may be consulted toprepare suitable preparations, without undue experimentation.

Various additives which enhance the stability and sterility of thecompositions, including antimicrobial preservatives, antioxidants,chelating agents, and buffers, can be added. Prevention of the action ofmicroorganisms can be ensured by various antibacterial and antifungalagents, for example, parabens, chlorobutanol, phenol, sorbic acid, andthe like. Prolonged absorption of the injectable pharmaceutical form canbe brought about by the use of agents delaying absorption, for example,alum inurn monostearate and gelatin. According to the present invention,however, any vehicle, diluent, or additive used would have to becompatible with the immunoresponsive cells expressing a generallyFcRL5-specific CAR of the presently disclosed subject matter.

The compositions can be isotonic, i.e., they can have the same osmoticpressure as blood and lacrimal fluid. The desired isotonicity of thecompositions of the presently disclosed subject matter may beaccomplished using sodium chloride, or other pharmaceutically acceptableagents such as dextrose, boric acid, sodium tartrate, propylene glycolor other inorganic or organic solutes. Sodium chloride is preferredparticularly for buffers containing sodium ions.

Viscosity of the compositions, if desired, can be maintained at theselected level using a pharmaceutically acceptable thickening agent.Methylcellulose can be used because it is readily and economicallyavailable and is easy to work with. Other suitable thickening agentsinclude, for example, xanthan gum, carboxymethyl cellulose,hydroxypropyl cellulose, carbomer, and the like. The concentration ofthe thickener can depend upon the agent selected. The important point isto use an amount that will achieve the selected viscosity. Obviously,the choice of suitable carriers and other additives will depend on theexact route of administration and the nature of the particular dosageform, e.g., liquid dosage form (e.g., whether the composition is to beformulated into a solution, a suspension, gel or another liquid form,such as a time release form or liquid-filled form).

Those skilled in the art will recognize that the components of thecompositions should be selected to be chemically inert and will notaffect the viability or efficacy of the immunoresponsive cells asdescribe in the presently disclosed subject matter. This will present noproblem to those skilled in chemical and pharmaceutical principles, orproblems can be readily avoided by reference to standard texts or bysimple experiments (not involving undue experimentation), from thisdisclosure and the documents cited herein.

One consideration concerning the therapeutic use of the immunoresponsivecells of the presently disclosed subject matter is the quantity of cellsnecessary to achieve an optimal effect. The quantity of cells to beadministered will vary for the subject being treated. In certainembodiments, from about 10⁴ to about 10¹⁰, from about 10⁵ to about 10⁹,or from about 10⁶ to about 10⁸ immunoresponsive cells of the presentlydisclosed subject matter are administered to a subject. More effectivecells may be administered in even smaller numbers. In certainembodiments, at least about 1×10⁸, about 2×10⁸, about 3×10⁸, about4×10⁸, and about 5×10⁸ immunoresponsive cells of the presently disclosedsubject matter are administered to a human subject. The precisedetermination of what would be considered an effective dose may be basedon factors individual to each subject, including their size, age, sex,weight, and condition of the particular subject. Dosages can be readilyascertained by those skilled in the art from this disclosure and theknowledge in the art.

The skilled artisan can readily determine the amount of cells andoptional additives, vehicles, and/or carrier in compositions and to beadministered in methods of the presently disclosed subject matter.Typically, any additives (in addition to the active cell(s) and/oragent(s)) are present in an amount of from about 0.001% to about 50% byweight) solution in phosphate buffered saline, and the active ingredientis present in the order of micrograms to milligrams, such as from about0.0001 wt % to about 5 wt %, from about 0.0001 wt % to about 1 wt %,from about 0.0001 wt % to about 0.05 wt %, from about 0.001 wt % toabout 20 wt %, from about 0.01 wt % to about 10 wt %, or from about 0.05wt % to about 5 wt %. For any composition to be administered to ananimal or human, and for any particular method of administration,toxicity should be determined, such as by determining the lethal dose(LD) and LD50 in a suitable animal model e.g., rodent such as mouse;and, the dosage of the composition(s), concentration of componentstherein and timing of administering the composition(s), which elicit asuitable response. Such determinations do not require undueexperimentation from the knowledge of the skilled artisan, thisdisclosure and the documents cited herein. And, the time for sequentialadministrations can be ascertained without undue experimentation.

VIII. Methods of Treatment

Tumor Microenvironment.

Tumors have a microenvironment that is hostile to the host immuneresponse involving a series of mechanisms by malignant cells to protectthemselves from immune recognition and elimination. This “hostile tumormicroenvironment” comprises a variety of immune suppressive factorsincluding infiltrating regulatory CD4⁺ T cells (Tregs), myeloid derivedsuppressor cells (MDSCs), tumor associated macrophages (TAMs), immunesuppressive cytokines including IL-10 and TGF-β, and expression ofligands targeted to immune suppressive receptors expressed by activatedT cells (CTLA-4 and PD-1). These mechanisms of immune suppression play arole in the maintenance of tolerance and suppressing inappropriateimmune responses, however within the tumor microenvironment thesemechanisms prevent an effective anti-tumor immune response. Collectivelythese immune suppressive factors can induce either marked anergy orapoptosis of adoptively transferred CAR modified T cells upon encounterwith targeted tumor cells.

Challenges in Tumor Immunology.

Effective tumor immunity requires recognition of tumor antigens andunopposed tumor elimination by immune effector cells. Tumor antigensmust contain peptide epitopes that are presented by the tumor and can berecognized by specific cytotoxic T lymphocytes (CTLs). The primed CTLsmust expand to a sufficient number and migrate to tumor sites, whereinthey mature into effectors to perform their functions, which areenhanced by helper T cells and dampened by Tregs and inhibitorymacrophages.

Targeted T Cell Therapy with Engineered T Lymphocytes.

T cell engineering is a groundbreaking strategy to potentially resolvemany previously observed shortcomings of earlier immunotherapeuticapproaches. Within the past year, researchers have reported dramaticcomplete remissions in relapsed (Brentjens et al., Blood 118, 4817-4828(2011) and Brentjens et al., Science translational medicine 5, 177ra138(2013)), chemorefractory leukemia and metastatic melanoma (Hunder etal., N. Engl. J. Med. 358, 2698-2703 (2008); Rosenberg et al., Nat. Rev.Cancer 8, 299-308 (2008); and Dudley et al., J Clin Oncol 26, 5233-5239(2008)), obtained with autologous peripheral blood T cells targeted to adefined antigen (CD19 and NY-ESO-1, respectively).

Rationale for a Genetic Approach:

Cell engineering can be used to redirect T cells toward tumor antigensand to enhance T cell function. One impetus for genetic T cellmodification is the potential to enhance T cell survival and expansionand to offset T cell death, anergy, and immune suppression. The genetictargeting of T cells can also be refined to prevent undesireddestruction of normal tissues.

Chimeric Antigen Receptors (CARs):

Tumor-specific t cells can be generated by the transfer of genes thatencode CARs (Brentjens et al., Clin. Cancer Res. 13, 5426-5435 (2007);Gade et al., Cancer Res. 65, 9080-9088 (2005); Maher et al., Nat.Biotechnol. 20, 70-75 (2002); Kershaw et al., J Immunol 173, 2143-2150(2004); Sadelain et al., Curr Opin Immunol (2009); and Hollyman et al.,J Immunother 32, 169-180 (2009)). Second-generation CARs comprise atumor antigen-binding domain fused to an intracellular signaling domaincapable of activating T cells and a co-stimulatory domain designed toaugment T cell potency and persistence (Sadelain et al., Cancerdiscovery 3, 388-398 (2013)). CAR design can therefore reconcile antigenrecognition with signal transduction, two functions that arephysiologically borne by two separate complexes, the TCR heterodimer andthe CD3 complex. The CAR's extracellular antigen-binding domain isusually derived from a murine monoclonal antibody (mAb) or fromreceptors or their ligands. Antigen recognition is therefore notMHC-restricted (Riviere et al., Curr Hematol Rep 3, 290-297 (2004); andStephan et al., Nat. Med. 13, 1440-1449 (2007)) and is thereforeapplicable to any patient expressing the target antigen, using the sameCAR. Antigen binding by the CARs triggers phosphorylation ofimmunoreceptor tyrosine-based activation motifs (ITAMs) in theintracellular domain, initiating a signaling cascade required forcytolysis induction, cytokine secretion, and proliferation. Because WICrestriction of antigen recognition is bypassed, the function ofCAR-targeted T cells is not affected by HLA downregulation or defects inthe antigen-processing machinery.

T Cell Requirements for Expansion and Survival:

Proliferation of tumor-specific T cells is needed ex vivo and isarguably desirable in vivo. T cell proliferation must be accompanied byT cell survival to permit absolute T cell expansion and persistence. Toproliferate in response to antigen, T cells must receive two signals.One is provided by TCR recognition of antigenic peptide/WIC complexesdisplayed on the surface of antigen-presenting cells (APCs) (Sadelain etal., Curr Opin Immunol (2009)). The other is provided by a T cellco-stimulatory receptor, such as the CD28 or 4-1BB receptors. Whereasthe cytolytic activity of T cells does not require concomitantco-stimulation, there is a critical need for the provision ofco-stimulatory signals to sustain the antitumor functions of adoptivelytransferred T cells, as previously demonstrated (Maher et al., Nat.Biotechnol. 20, 70-75 (2002); Sadelain et al., Cancer discovery 3,388-398 (2013); Krause et al., J Exp Med 188, 619-626 (1998); Gong etal., Neoplasia. 1, 123-127 (1999); and Lyddane et al., J. Immunol. 176,3306-3310 (2006)).

Immune Monitoring:

Lymphocytes are multifunctional “drugs” that exhibit dynamicallyevolving effects after infusion. Upon antigen encounter, tumor-specificT cells activate and/or release a variety of proteins that can triggertumor killing, T cell proliferation, and recruitment or immunomodulationof other immune cells. Thus, measuring which proteins are secreted fromwhich cells, in what quantity, and at what time point yields profoundinsights into why a particular patient is or is not responding andprovides critical feedback for designing more-effective trials. Theseassay systems will permit direct and meaningful comparisons of clinicalapproaches and thus help design rational, next-generation therapeuticstrategies.

For treatment, the amount administered is an amount effective inproducing the desired effect. An effective amount can be provided in oneor a series of administrations. An effective amount can be provided in abolus or by continuous perfusion.

An “effective amount” (or, “therapeutically effective amount”) is anamount sufficient to affect a beneficial or desired clinical result upontreatment. An effective amount can be administered to a subject in oneor more doses. In terms of treatment, an effective amount is an amountthat is sufficient to palliate, ameliorate, stabilize, reverse or slowthe progression of the disease, or otherwise reduce the pathologicalconsequences of the disease. The effective amount is generallydetermined by the physician on a case-by-case basis and is within theskill of one in the art. Several factors are typically taken intoaccount when determining an appropriate dosage to achieve an effectiveamount. These factors include age, sex and weight of the subject, thecondition being treated, the severity of the condition and the form andeffective concentration of the immunoresponsive cells administered.

For adoptive immunotherapy using antigen-specific T cells, cell doses inthe range of about 10⁶ to about 10¹⁰ (e.g., about 10⁹) are typicallyinfused. Upon administration of the immunoresponsive cells into thesubject and subsequent differentiation, the immunoresponsive cells areinduced that are specifically directed against one specific antigen(e.g., FcRL5). “Induction” of T cells can include inactivation ofantigen-specific T cells such as by deletion or anergy. Inactivation isparticularly useful to establish or reestablish tolerance such as inautoimmune disorders. The immunoresponsive cells of the presentlydisclosed subject matter can be administered by any methods known in theart, including, but not limited to, pleural administration, intravenousadministration, subcutaneous administration, intranodal administration,intratumoral administration, intrathecal administration, intrapleuraladministration, intraperitoneal administration, and directadministration to the thymus. In certain embodiments, theimmunoresponsive cells and the compositions comprising thereof areintravenously administered to the subject in need.

The presently disclosed subject matter provides various methods of usingthe immunoresponsive cells (e.g., T cells) expressing a FcRL5-specificCAR. For example, the presently disclosed subject matter providesmethods of reducing tumor burden in a subject. In one non-limitingexample, the method of reducing tumor burden comprises administering aneffective amount of the presently disclosed immunoresponsive cell to thesubject, thereby inducing tumor cell death in the subject. The presentlydisclosed immunoresponsive cell can reduce the number of tumor cells,reduce tumor size, and/or eradicate the tumor in the subject.Non-limiting examples of suitable tumors include multiple myeloma,Non-Hodgkin Lymphoma (especially Mantle Cell), Hodgkin Lymphoma, ChronicLymphocytic Leukemia (CLL), Acute lymphocytic leukemia (ALL), Hairy CellLeukemia, Burketts Lymphoma, and Waldenstrom's Macroglobulinemia.

The presently disclosed subject matter also provides methods ofincreasing or lengthening survival of a subject having a neoplasia. Inone non-limiting example, the method of increasing or lengtheningsurvival of a subject having neoplasia comprises administering aneffective amount of the presently disclosed immunoresponsive cell to thesubject, thereby increasing or lengthening survival of the subject. Themethod can reduce or eradicate tumor burden in the subject. Thepresently disclosed subject matter further provides methods for treatingor preventing a neoplasia in a subject, comprising administering thepresently disclosed immunoresponsive cell to the subject.

As used herein, the term “neoplasia” refers to a disease characterizedby the pathological proliferation of a cell or tissue and its subsequentmigration to or invasion of other tissues or organs. Neoplasia growth istypically uncontrolled and progressive, and occurs under conditions thatwould not elicit, or would cause cessation of, multiplication of normalcells. Neoplasias can affect a variety of cell types, tissues, ororgans, including but not limited to an organ selected from the groupconsisting of bladder, colon, bone, brain, breast, cartilage, glia,esophagus, fallopian tube, gallbladder, heart, intestines, kidney,liver, lung, lymph node, nervous tissue, ovaries, pleura, pancreas,prostate, skeletal muscle, skin, spinal cord, spleen, stomach, testes,thymus, thyroid, trachea, urogenital tract, ureter, urethra, uterus, andvagina, or a tissue or cell type thereof. Neoplasias include cancers,such as sarcomas, carcinomas, or plasmacytomas (malignant tumor of theplasma cells).

Cancers whose growth may be inhibited using the immunoresponsive cellsof the presently disclosed subject matter comprise cancers typicallyresponsive to immunotherapy. Non-limiting examples of cancers fortreatment include multiple myeloma, Non-Hodgkin Lymphoma (especiallyMantle Cell), Hodgkin Lymphoma, Chronic Lymphocytic Leukemia (CLL),Acute lymphocytic leukemia (ALL), Hairy Cell Leukemia, BurkettsLymphoma, and Waldenstrom's Macroglobulinemia. In certain embodiments,the cancer is multiple myeloma.

Additionally, the presently disclosed subject matter provides methods ofincreasing immune-activating cytokine production in response to a cancercell in a subject. In one non-limiting example, the method comprisesadministering the presently disclosed immunoresponsive cell to thesubject. The immune-activating cytokine can be granulocyte macrophagecolony stimulating factor (GM-CSF), IFN-α, IFN-β, IFN-γ, TNF-α, IL-2,IL-3, IL-6, IL-11, IL-7, IL-12, IL-15, IL-21, interferon regulatoryfactor 7 (IRF7), and combinations thereof. In certain embodiments, theimmunoresponsive cells including an FcRL5-specific CAR of the presentlydisclosed subject matter increase the production of GM-CSF, IFN-γ,and/or TNF-α.

Suitable human subjects for therapy typically comprise two treatmentgroups that can be distinguished by clinical criteria. Subjects with“advanced disease” or “high tumor burden” are those who bear aclinically measurable tumor (e.g., multiple myeloma). A clinicallymeasurable tumor is one that can be detected on the basis of tumor mass(e.g., by palpation, CAT scan, sonogram, mammogram or X-ray; positivebiochemical or histopathologic markers on their own are insufficient toidentify this population). A pharmaceutical composition embodied in thepresently disclosed subject matter is administered to these subjects toelicit an anti-tumor response, with the objective of palliating theircondition. Ideally, reduction in tumor mass occurs as a result, but anyclinical improvement constitutes a benefit. Clinical improvementcomprises decreased risk or rate of progression or reduction inpathological consequences of the tumor (e.g., multiple myeloma).

A second group of suitable subjects is known in the art as the “adjuvantgroup.” These are individuals who have had a history of neoplasia (e.g.,multiple myeloma), but have been responsive to another mode of therapy.The prior therapy can have included, but is not restricted to, surgicalresection, radiotherapy, and traditional chemotherapy. As a result,these individuals have no clinically measurable tumor. However, they aresuspected of being at risk for progression of the disease, either nearthe original tumor site, or by metastases. This group can be furthersubdivided into high-risk and low-risk individuals. The subdivision ismade on the basis of features observed before or after the initialtreatment. These features are known in the clinical arts, and aresuitably defined for each different neoplasia. Features typical ofhigh-risk subgroups are those in which the tumor (e.g., multiplemyeloma) has invaded neighboring tissues, or who show involvement oflymph nodes. Another group has a genetic predisposition to neoplasia(e.g., multiple myeloma) but has not yet evidenced clinical signs ofneoplasia (e.g., multiple myeloma). For instance, women testing positivefor a genetic mutation associated with breast cancer, but still ofchildbearing age, can wish to receive one or more of the antigen-bindingfragments described herein in treatment prophylactically to prevent theoccurrence of neoplasia until it is suitable to perform preventivesurgery.

The subjects can have an advanced form of disease (e.g., multiplemyeloma), in which case the treatment objective can include mitigationor reversal of disease progression, and/or amelioration of side effects.The subjects can have a history of the condition, for which they havealready been treated, in which case the therapeutic objective willtypically include a decrease or delay in the risk of recurrence.

Further modification can be introduced to the FcRL5-specificCAR-expressing immunoresponsive cells (e.g., T cells) to avert orminimize the risks of immunological complications (known as “malignantT-cell transformation”), e.g., graft versus-host disease (GvHD), or whenhealthy tissues express the same target antigens as the tumor cells,leading to outcomes similar to GvHD. A potential solution to thisproblem is engineering a suicide gene into the CAR-expressing T cells.Suitable suicide genes include, but are not limited to, Herpes simplexvirus thymidine kinase (hsv-tk), inducible Caspase 9 Suicide gene(iCasp-9), and a truncated human epidermal growth factor receptor(EGFRt) polypeptide. In certain embodiments, the suicide gene is anEGFRt polypeptide. The EGFRt polypeptide can enable T cell eliminationby administering anti-EGFR monoclonal antibody (e.g., cetuximab). EGFRtcan be covalently joined to the 3′ terminus of the intracellular domainof the FcRL5-specific CAR. The suicide gene can be included within thevector comprising nucleic acids encoding the presently disclosedFcRL5-specific CARs. In this way, administration of a prodrug designedto activate the suicide gene (e.g., a prodrug (e.g., AP1903 that canactivates iCasp-9) during malignant T-cell transformation (e.g., GVHD)triggers apoptosis in the suicide gene-activated CAR-expressing T cells.

IX. Kits

The presently disclosed subject matter provides kits for the treatmentor prevention of a neoplasia (e.g., multiple myeloma). In certainembodiments, the kit comprises a therapeutic or prophylactic compositioncontaining an effective amount of an immunoresponsive cell comprising aFcRL5-specific CAR in unit dosage form. In particular embodiments, thecells further expresses at least one co-stimulatory ligand. In certainembodiments, the kit comprises a sterile container which contains atherapeutic or prophylactic vaccine; such containers can be boxes,ampules, bottles, vials, tubes, bags, pouches, blister-packs, or othersuitable container forms known in the art. Such containers can be madeof plastic, glass, laminated paper, metal foil, or other materialssuitable for holding medicaments.

If desired, the immunoresponsive cell is provided together withinstructions for administering the cell to a subject having or at riskof developing a neoplasia (e.g., multiple myeloma). The instructionswill generally include information about the use of the composition forthe treatment or prevention of a neoplasia (e.g., multiple myeloma). Inother embodiments, the instructions include at least one of thefollowing: description of the therapeutic agent; dosage schedule andadministration for treatment or prevention of a neoplasia (e.g.,multiple myeloma) or symptoms thereof; precautions; warnings;indications; counter-indications; overdosage information; adversereactions; animal pharmacology; clinical studies; and/or references. Theinstructions may be printed directly on the container (when present), oras a label applied to the container, or as a separate sheet, pamphlet,card, or folder supplied in or with the container.

X. Exemplary Extracellular Antigen-Binding Domains (e.g., scFvs)

TABLE 1 ET200-001 DNA Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag)Cagtctgtgttgacgcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggt [SEQID NO: 1]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ ID NO: 305]caggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtgtatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcgaaggtccgtacgacggtttcgattcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 2]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag) QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVL G [SEQ ID NO: 3]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGPYDGFDSWGQGTLVTVSS [SEQ ID NO: 4] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 2 ET200-002 DNA Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag)Aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattctgtggtattcggcggagggaccaagctgaccgtcctaggt[SEQ ID No. 5]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ ID NO: 305]caggtccagctggtacagtctggcactgaggtgaagaagcctggggcctcagtgagggtcgcctgcaaggcttctggttacccctttaacaaatatgacatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggaggcatcatccctatctttcgtacaacaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtatattactgtgcgcgcgaatggttctactgggatatctggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 6]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag) NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNSVVFGGGTKLTVLG [SEQ ID NO: 7]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGTEVKKPGASVRVACKASGYPFNKYDINWVRQAPGQGLEWMGGIIPIFRTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREWFYWDIWGQGTLVTVSS [SEQ ID NO: 8] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 3 ET200-003 DNA Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag)cagtctgtgttgactcagccaccctcagtgtccgtgtccccaggacagacagccagcatctcctgctctggaaataaattggggactaagtatgtttactggtatcagaagaggccaggccagtcccctgtgttggtcatgtatgaagataatcagcggccctcagggatcccggagcggttctctggctccaactctgggaacacagccactctgaccatcagagggacccagactgtggatgaggctgactattactgtcaggcgtgggactccgacactttcgtggtcttcggcggagggaccaaggtcaccgtcctaggt [SEQ ID NO:9]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ ID NO: 305]gaggtgcagctggtggagaccgggggaggcgtggtccagcctgggaggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatggcatgcactgggtccgccaggctccaggcaaggggctggagtgggtggcagttatatcacatgatggaagtaataaatactacgcagactccgtgaagggccgattcaccatctccagagacaattccaaggacacgctgtatctgcaaatgaacagcctgagaggtgaggacacggccgtatattactgtgcgcgctctaaccagtggtctggttacttctctttcgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 10]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag) QSVLTQPPSVSVSPGQTASISCSGNKLGTKYVYWYQKRPGQSPVLVMYEDNQRPSGIPERFSGSNSGNTATLTIRGTQTVDEADYYCQAWDSDTFVVFGGGTKVTVLG [SEQ ID NO: 11]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVETGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISHDGSNKYYADSVKGRFTISRDNSKDTLYLQMNSLRGEDTAVYYCARSNQWSGYFSFDYWGQGTLVTVSS [SEQ ID NO: 12]TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 4 ET200-006 DNA Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag)tcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtggtggtcatccattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggt [SEQID NO: 13]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ ID NO: 305]gaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccacctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcaacacttacaatggtcacacaaactatgcacagaagctccagggcagagccacaatgaccgcagacacatccacgaacacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgcgttatctacggttctggtgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 14]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag) SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVVVIHYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLG [SEQ ID NO: 15] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGISWVRQAPGQGLEWMGWINTYNGHTNYAQKLQGRATMTADTSTNTAYMELRSLRSDDTAVYYCARVIYGSGDYWGQGTLVTVSS [SEQ ID NO: 16]TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 5 ET200-007 DNA Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag)tcctatgtgctgactcagccactctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaactgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatcgggtgttcggcggagggaccaagctgaccgtcctaggt [SEQID NO: 17]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ ID NO: 305]caggtgcagctgcaggagtcgggcccaggactggtgaagccttcggagaccctgtccctcacctgcaatgtctctggttactccatcagcagtggttacttttggggctggatccggcagcccccagggaaggggctggagtggattgggagtatctatcatagtaggagcacctactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgaactctgtgaccgccgcagacacggccgtgtattactgtgcgcgcggttacggttacttcgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 18]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence(light chain variable region scFv linker heavy chain variable region His tag +HA tag) SYVLTQPLSVSVAPGKTARITCGGNNIGSKTVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHRVFGGGTKLTVLG [SEQ ID NO: 19]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQESGPGLVKPSETLSLTCNVSGYSISSGYFWGWIRQPPGKGLEWIGSIYHSRSTYYNPSLKSRVTISVDTSKNQFSLKLNSVTAADTAVYYCARGYGYFDYWGQGTLVTVSS [SEQ ID NO: 20] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 6 ET200-008 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caatctgccctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactatgtctcctggtaccaacaacacccaggcaaagcccccaaactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcacttcgaaggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 21]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggaggtgtggtacggcctggggggtccctgagactctcctgtgcagcctctggattcacctttggtgattatggcatgagctgggtccgccaagctccagggaaggggctggagtgggtctctggtattaattggaatggtggtagcacaggttatgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagccgaggacacggccgtatattactgtgcgcgctctaaatacaacttccatgtttactacgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 22]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTSKVFGGGTKLTVL G [SEQ ID NO:23] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGGVVRPGGSLRLSCAASGFTFGDYGMSWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSKYNFHVYYDYWGQGTLVTVSS [SEQ ID NO: 24] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 7 ET200-009 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccaccctcagcgtctgggacccccgggcagacagtcaccatctcttgttctggaagcaactccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcctcatctataggaataatcagcggccctcaggggtccctgaccgattctcaggctccaagtctggcacctcagcctccctggccatcagtgggctccgctccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtgcttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 25]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgctcttctggtaacatggtttcttggaaagatatgtggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 26]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSASGTPGQTVTISCSGSNSNIGSNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSAYVFGTGTKVTVL G [SEQ ID NO:27] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARSSGNMVSWKDMWGQGTLVTVSS [SEQ ID NO: 28] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 8 ET200-010 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caatctgccctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactctgtctcctggtaccaacaacacccaggcaaagcccccagactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcacccctttagtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 29]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcggtgctgttgcttaccatgattggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 30]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSALTQPASVSGSPGQSITISCTGTSSDVGGYNSVSWYQQHPGKAPRLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTPLVFGTGTKVTVL G [SEQ ID NO:31] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGAVAYHDWGQGTLVTVSS [SEQ ID NO: 32] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO:308]

TABLE 9 ET200-011 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagagggtcaccatctcctgctctggaagcagctccaacatttcgatttatgatgtatcctggtatcagcagctcccaggaacagcccccaaactcctcatttatggcaataataagcgaccctcggggattgctgaccgattctctggctccacgtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatgacagtctgagtgggggggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 33]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]cagatgcagctggtgcaatctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcgaggcttctggaggcaccctcagcagctatgctatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatgtttggtacagcacactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgaaaacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtgttcattacgcttctttcgatcattggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 34]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSAAPGQRVTISCSGSSSNISIYDVSWYQQLPGTAPKLLIYGNNKRPSGIADRFSGSTSGTSATLGITGLQTGDEADYYCGTWDDSLSGGVFGGGTKLTVLG [SEQ ID NO: 35]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QMQLVQSGAEVKKPGSSVKVSCEASGGTLSSYAINWVRQAPGQGLEWMGGIIPMFGTAHYAQKFQGRVTITADESTKTAYMELSSLRSEDTAVYYCARGVHYASFDHWGQGTLVTVSS [SEQ ID NO: 36] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO:308]

TABLE 10 ET200-012 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctgcggccgcaggacagaaggtcaccatctcctgctctggaagcgactccaacattgggaataattatgtgtcctggtatcaacacctcccagggacagcccccaaactcctcatttatgacgttaaaaatcgaccctcagggattcctgaccggttctccggctccaagtctggctcgtcagccaccctaggcatcgccggactccagcctggggacgaggccgattattactgcggaacatgggacagtcggctggatgcctatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 37]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]cagatgcagctggtgcaatctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaagacttctggtttcccctttaatatctttggaatcacctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcggttacaacggtaacacagactacccacagaagttccagggcagagtcaccatgtccacagacacatccacgagtacagcctacatggagctgaggaacctgaaatctgacgacacggccgtgtattactgtgcgcgcggtgcttacggtggtatggatacttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 38]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSAAAGQKVTISCSGSDSNIGNNYVSWYQHLPGTAPKLLIYDVKNRPSGIPDRFSGSKSGSSATLGIAGLQPGDEADYYCGTWDSRLDAYVFGTGTKVTVL G [SEQ ID NO:39] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QMQLVQSGAEVKKPGASVKVSCKTSGFPFNIFGITWVRQAPGQGLEWMGWISGYNGNTDYPQKFQGRVTMSTDTSTSTAYMELRNLKSDDTAVYYCARGAYGGMDTWGQGTLVTVSS [SEQ ID NO: 40] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO:308]

TABLE 11 ET200-013 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcacctccaacatcggggcaggttatgatgtacactggtatcagcagcttccaggaacagcccccaaactcctcatctatactaacaactttcggccctcaggggtccctgaccgattctctgcctccaagtctggcacttcagcttccctggccatcactggtctccaggctgaggatgaggctgattattactgcggaacatgggatagcagcctgagtgccgttgtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 41]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctggaactgaggtgaagaagcctggggcctcagtgaaagtctcctgcaaggcttctggttacatgtttaccagttatggtctcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgctaacaatggtaagacaaattatgctaagaaattccaggacagagtcaccatgaccagagacacttccacgagcacaggctacatggaactgaggagcctgagatctgacgacacggccgtatattactgtgcgcgccatatcggtggttcttacttcgatcgttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 42]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSGAPGQRVTISCTGSTSNIGAGYDVHWYQQLPGTAPKLLIYTNNFRPSGVPDRFSASKSGTSASLAITGLQAEDEADYYCGTWDSSLSAVVFGGGTKLT VLG [SEQ ID NO:43] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGTEVKKPGASVKVSCKASGYMFTSYGLNWVRQAPGQGLEWMGWISANNGKTNYAKKFQDRVTMTRDTSTSTGYMELRSLRSDDTAVYYCARHIGGSYFDRWGQGTLVTVSS [SEQ ID NO: 44] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO:308]

TABLE 12 ET200-014 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcattatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 45]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagactgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtgatggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagacgaggacacggccgtatattactgtgcgcgctctcatgaagctaacctggttggtgattggtggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 46]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKVTVLG [SEQ ID NO: 47]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSDGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSHEANLVGDWWGQGTLVTVSS [SEQ ID NO: 48] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO:308]

TABLE 13 ET200-015 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtggtgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatgtggtattcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 49]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctacggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgctggggtggtttcggtgctgttgatcattggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 50]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDVVFGGGTKLTVLG [SEQ ID NO: 51]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARWGGFGAVDHWGQGTLVTVSS [SEQ ID NO: 52] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO:308]

TABLE 14 ET200-016 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcttctgagctgactcaggaccctgctgtgtctgtggccttgggacagacagtcaagatcacgtgccaaggagacagcctcacagactaccatgcaacctggtaccagcagaagccaggacaggcccctgtcgctgtcatctatgctacaaacaaccggcccactgggatcccagaccgattctctggttccagttccggaaacacagcttctttgaccatcactggggctcaggcggaagatgaggctgactattactgtaattcccgggacagcggcacggacgaagtgttattcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 53]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagactgggggaggcctggtcaagcctggggggtccctgagactctcctgtgcagcctctggattcaccttcagtagctatagcatgaactgggtccgccaggctccagggaaggggctggagtgggtctcatccattagtagtagtagtagttacatatactacgcagactcagtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggccgtgtattactgtgcgcgcggtcagggttacgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 54]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SSELTQDPAVSVALGQTVKITCQGDSLTDYHATWYQQKPGQAPVAVIYATNNRPTGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSGTDEVLFGGGTKLTVLG [SEQ ID NO: 55]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVETGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGQGYD YWGQGTLVTVSS [SEQID NO: 56] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 15 ET200-017 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcgtctatgatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgagcatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatactgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 57]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgctactacccgggtatggatatgtggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 58]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLSISRVEAGDEADYYCQVWDSSSDHTVFGTGTKVTVLG [SEQ ID NO: 59]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARYYPGMD MWGQGTLVTVSS [SEQID NO: 60] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 16 ET200-018 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagccgccctcaacgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcgggagaaatggtgtaaactggtaccagcagctcccaggagcggcccccaaagtcctcatctataatgataatcagcgaccctcaggggtccctgaccgagtctctggctcccagtctggctcctcaggcaccctggccatcgatgggcttcggtctgaggatgaggctgattattactgtgcggcatgggatgacagcctgcatggtgtggtattcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 61]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtccagctggtacagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcaatgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtggttacggtgattcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 62]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSTSGTPGQRVTISCSGSSSNIGRNGVNWYQQLPGAAPKVLIYNDNQRPSGVPDRVSGSQSGSSGTLAIDGLRSEDEADYYCAAWDDSLHGVVFGGGTKLTV LG [SEQ ID NO:63] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKVSGYTLNELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARGG YGDSWGQGTLVTVSS [SEQID NO: 64] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 17 ET200-019 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattcttgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 65]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcaatctggggctgaggtgaagaggcctgggtcctcggtgaaggtctcctgcacggcttctggaggcaccttcagcagcgatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggaggaatcatccctatgtttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcgaaggttactactacccgtctgcttacctgggttctgttctgaacgacatctcttctgtttacgatgaatggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 66] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNSWVFGGGTKLTVL G [SEQ ID NO:67] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKRPGSSVKVSCTASGGTFSSDAISWVRQAPGQGLEWMGGIIPMFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYPSAYLGSVLNDISSVYDEWGQGTLVTVSS [SEQ ID NO: 68] TSGQAGQHHHHHHGAYPYDVPDYAS[SEQ ID NO: 308]

TABLE 18 ET200-020 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcacctccaacattggaaataatgatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcgtgagtgcttcttgggtcttcggcagagggaccaagctgaccgtcctaggt[SEQ ID NO: 69]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatccacagaagctccagggcagagtcaccatgaccacagacccatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgctctatgacttctttcgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 70]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSAAPGQKVTISCSGSTSNIGNNDVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSVSASWVFGRGTKLTV LG [SEQ ID NO:71] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYPQKLQGRVTMTTDPSTSTAYMELRSLRSDDTAVYYCARSMTSFDYWGQGTLVTVSS [SEQ ID NO: 72] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO:308]

TABLE 19 ET200-021 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcaactccaacattgggaataattatgtatcctggtatcagcaactcccagggacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaggtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatggaataccactgtgactcctggctatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 73]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaagtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacaccgccatgtattactgtgcgcgctctgtttacgacctggatacttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 74]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSAAPGQKVTISCSGSNSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSRSGTSATLGITGLQTGDEADYYCGTWNTTVTPGYVFGTGTKVTV LG [SEQ ID NO:75] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAMYYCARSVY DLDTWGQGTLVTVSS [SEQID NO: 76] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 20 ET200-022 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgggggccccttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 77]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtgcagtcttggggaggctcggaacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagcggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaattccctgtatctgcaaatgaacagtctgagagctgaggacaccgccatgtattactgtgcgcgctaccgtcaggttggttctgcttacgattcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 78]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLGAPYVFGTGTKVTV LG [SEQ ID NO:79] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSWGGSEQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAMYYCARYRQVGSAYDSWGQGTLVTVSS [SEQ ID NO: 80] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 21 ET200-023 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)ctgcctgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtatcagcagaagccaggccaggcccctgtgctggtcgtctatgctgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagttatcataattatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 81]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgagcagcctgagatctgaggacaccgccatgtattactgtgcgcgctactggggtttcggtgtttctgatcgttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 82]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) LPVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYADSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSYHNYVFGTGTKVTVL G [SEQ ID NO:83] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELSSLRSEDTAMYYCARYW GFGVSDRWGQGTLVTVSS[SEQ ID NO: 84] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 22 ET200-024 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccccgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgacagcagcaatctttgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 85]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]cagatgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctacaactactactactacgattcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 86]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNLWVFGGGTKLTVL G [SEQ ID NO:87] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QMQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARYNYYY YDSWGQGTLVTVSS[SEQ ID NO: 88] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 23 ET200-025 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)gacatccagatgacccagtctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagtcagagcattagcagctatttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctatgctgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttactactgtcaacagagttacagtaccccattcactttcggccctgggaccaaagtggatatcaaacgt [SEQID NO: 89]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacaccgccatgtattactgtgcgcgctactggggttacgactcttacgatgaatggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 90]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIKR [SEQ ID NO: 91]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAMYYCARYWGYD SYDEWGQGTLVTVSS[SEQ ID NO: 92] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 24 ET200-026 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 93]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcaacaaccattactacaacgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 94]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVL G [SEQ ID NO:95] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARNNHYY NDYWGQGTLVTVSS [SEQID NO: 96] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 25 ET200-027 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagggggtcaccatcccctgcactgggagcagctccaacatcggggcaggttatgatgtacactggtaccagcagcttccagggacagcccccaaactcctcatctatggtaacaacaatcggccctcaggggtccctgaccgcttctctggctccaggtctggctcctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtgatgtggtattcggcggagggaccaaggtcaccgtcctaggt[SEQ ID NO: 97]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggggctgaggtgaagaagcctggggctacagtgaaaatctcctgcaaggtttctggatacaccttcaccgactactacatgcactgggtgcaacaggcccctggaaaagggcttgagtggatgggacttgttgatcctgaagatggtgaaacaatatacgcagagaagttccagggcagagtcaccataaccgcggacacgtctacagacacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgctactggtcttactctttcgactacctgtacatgccggaaggtaacgattggtggggtcaaggtactctggtgaccgtctcctca [SEQ IDNO: 98] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSGAPGQGVTIPCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSRSGSSASLAITGLQAEDEADYYCQSYDSSLSDVVFGGGTKVTV LG [SEQ ID NO:99] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGATVKISCKVSGYTFTDYYMHWVQQAPGKGLEWMGLVDPEDGETIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCARYWSYSFDYLYMPEGNDWWGQGTLVTVSS [SEQ ID NO: 100] TSGQAGQHHHHHHGAYPYDVPDYAS[SEQ ID NO: 308]

TABLE 26 ET200-028 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgactcagccacccgcagcgtctgggacccccggacagagagtcaccatctcttgttctgggggcgtctccaacatcgggagtggtgctctaaattggtaccagcaactcccaggaacggcccccaaactcctcatctatagttacaatcagcggccctcaggggtctctgaccgattctctggctccaggtctgccacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcaacctgggatgatagtgtgaatggttgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 101]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtccagctggtacagtctggagctgaggtgaagaagcctggggattcagtgaaggtctcctgcaagccttctggttacaattttctcaactatggtatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggattagcacttacaccggtaacacaaactatgcacagaagctgcagggcagagtcaccttcaccacagacacatccacgagcacagcctacatggagatgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcgacctgtactactacgaaggtgttgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 102]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPAASGTPGQRVTISCSGGVSNIGSGALNWYQQLPGTAPKLLIYSYNQRPSGVSDRFSGSRSATSASLAISGLQSEDEADYYCATWDDSVNGWVFGGGTKLTV LG [SEQ ID NO:103] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGDSVKVSCKPSGYNFLNYGINWVRQAPGQGLEWMGWISTYTGNTNYAQKLQGRVTFTTDTSTSTAYMEMRSLRSDDTAVYYCARDLYYYEG VDYWGQGTLVTVSS[SEQ ID NO: 104] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 27 ET200-029 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccagggttacctgtgggggaaacaacattggaagtgaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgttggtcatctattatgataccgaccggccctcagggatccctgagcgattctctggctcccactctgggaccacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagggatcatgtggtattcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 105]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctgggggaggcgtggtccagcctgggaggtccctgagactctcctgtgcggcctctggattcaccttcagtagctatgctatgcactgggtccgccaggctccaggcaagggactggagtgggtggcagttatatcatatgatggaagcaataaatactacgcagactccgtgaagggcctattcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagctgaggacacggccgtgtattactgtgcgcgctcttacttcacttctggtttctacgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 106]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSVSVAPGKTARVTCGGNNIGSESVHWYQQKPGQAPVLVIYYDTDRPSGIPERFSGSHSGTTATLTISRVEAGDEADYYCQVWDSSRDHVVFGGGTKLTVLG [SEQ ID NO: 107]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGLFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYFT SGFYDYWGQGTLVTVSS[SEQ ID NO: 108] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 28 ET200-030 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagttccaacatcggggcaggttatgatgtaaattggtatcagcagtttccaggaacagcccccaaactcctcatctatggtaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggctcttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 109]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]cagatgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcatgtcttctatgtactacgattggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 110]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVNWYQQFPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGSYVFGTGTKVT VLG [SEQ ID NO:111] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QMQLVQSGAEVKKPGASVKVSCKASGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARMS SMYYDWGQGTLVTVSS[SEQ ID NO: 112] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 29 ET200-031 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgattatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 113]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagactgggggaggcttggtcaagcctggagggtccctgagactctcctgtgcagcctctggattcaccgtcagtgactactacatgagctggatccgccaggctccagggaagggcctggagtggatttcatacattagtggtagtggtaatagcatatactacgcagactctgtgaagggccgattcaccatctccagggacaacgccaagaactcactggatctgcaaatgaccagcctgagagccgaggacacggccgtatattactgtgcgcgctctactaaattcgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 114]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDYVFGTGTKVTVLG [SEQ ID NO: 115]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVETGGGLVKPGGSLRLSCAASGFTVSDYYMSWIRQAPGKGLEWISYISGSGNSIYYADSVKGRFTISRDNAKNSLDLQMTSLRAEDTAVYYCARSTKFDY WGQGTLVTVSS [SEQ IDNO: 116] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 30 ET200-032 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)ctgcctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacgtcggaagttacactgtaaactggtaccggcaactcccaggaacggcccccacactcctcatctataataataatcagcggccctcaggggtccctgaccgattctctgactccaagtctggcacctcggcctccctgaccattagtgggctccagcctgaggatgaggctgattattattgtgcagcatgggatgacaggctgggtggttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 117]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtgcagtctggagcagaggtgaaaaagccgggggagtctctgaagatctcctgtaagggttctggatacagctttaccaactactggatcggctgggtgcgccagatgcccgggaaaggcctggagtggatggggatcatctatcctggtgactctgataccagatacagcccgtccttccaaggccaggtcaccatctcagccgacaagtccatcagcaccgcctacctacagtggagcagcctgaaggcctcggacaccgccatgtattactgtgcgcgctctactggttcttctcatatgtctgatgaatggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 118]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) LPVLTQPPSASGTPGQRVTISCSGSSSNVGSYTVNWYRQLPGTAPTLLIYNNNQRPSGVPDRFSDSKSGTSASLTISGLQPEDEADYYCAAWDDRLGGYVFGTGTKVTVL G [SEQ ID NO:119] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARSTGSS HMSDEWGQGTLVTVSS[SEQ ID NO: 120] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 31 ET200-033 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaatcattgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 121]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caagtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggagatcactcatagtggaaggtccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgctcttctatcatgtctgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 122]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNHWVFGGGTKLTV LG [SEQ ID NO:123] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEITHSGRSNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSSIMSDY WGQGTLVTVSS [SEQID NO: 124] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 32 ET200-034 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcacctccaacatcggggcaggttatgatgtacactggtaccagcagcttccaggaacagcccccaaactcctcatcaacaataacaggaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatggcagcctgactggtgcagtgttcggcggagggaccaagctgaccgtcctaggt [SEQ ID NO: 125]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcatgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcggttctgctctggaccattacgatcgttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 126]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSGAPGQRVTISCTGSTSNIGAGYDVHWYQQLPGTAPKLLINNNRNRPSGVPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDGSLTGAVFGGGTKLT VLG [SEQ ID NO:127] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSALDH YDRWGQGTLVTVSS[SEQ ID NO: 128] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 33 ET200-035 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcaccaattgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 129]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctacaactactacttcaacgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 130]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTNWVFGGGTKLTVLG [SEQ ID NO: 131]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARYNYYFN DYWGQGTLVTVSS [SEQID NO: 132] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 34 ET200-037 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 133]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]cagatgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgctctatgttcggtgctcatgattcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 134]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLG [SEQ ID NO: 135]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QMQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARS MFGAHDSWGQGTLVTVSS[SEQ ID NO: 136] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 35 ET200-038 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaacatcggggcaggttttgatgtacactggtaccagctacttccaggaacagcccccaaactcctcatctatgctaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctcctggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggtgtggtattcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 137]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcaatctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtgcttctttcgaccgtcatgataactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 138]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGFDVHWYQLLPGTAPKLLIYANSNRPSGVPDRFSGSKSGTSASLAITGLLAEDEADYYCQSYDSSLSGVVFGGGTKLTV LG [SEQ ID NO:139] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGASFDR HDNWGQGTLVTVSS[SEQ ID NO: 140] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 36 ET200-039 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagttcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 141]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgctctaactactactacaacgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 142]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVLG [SEQ ID NO: 143]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSNYYYN DYWGQGTLVTVSS [SEQID NO: 144] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 37 ET200-040 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaacatcggggcaggttatgatgtacactggtaccagcagcttccaggaacagcccccaaactcctcatctatggtaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 145]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctactctggtgtttactacgattggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 146]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGYVFGTGTKVTV LG [SEQ ID NO:147] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARYS GVYYDWGQGTLVTVSS[SEQ ID NO: 148] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 38 ET200-041 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggggtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccgacaactttgtgcagtggtaccagcagcgcccgggcggtgtccccaccactgtgatctttaatgatgacgaaagaccctctggcgtccctgatcggttctctggctccatcgacacctcctccaattctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgataataataatcgaggggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 149]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatgaaccctaacagtggtaacacaggctatgcacagaagttccagggcagagtcaccatgaccaggaacacctccataagcacagcctacatggagctgagcaacctgagatctgaggacacggccgtgtattactgtgcgcgctactactcttacggttacgattggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 150]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSGSPGKTVTISCTGSSGSIADNFVQWYQQRPGGVPTTVIFNDDERPSGVPDRFSGSIDTSSNSASLTISGLKTEDEADYYCQSYDNNNRGVFGGGTKLTV LG [SEQ ID NO:151] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRNTSISTAYMELSNLRSEDTAVYYCARYYS YGYDWGQGTLVTVSS [SEQID NO: 152] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 39 ET200-042 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagacggtcaccatctcctgcactgggggcagctccaacatcgggacaggttattttgtaaattggtaccagcaggttccaggaaaagcccccaaactcctcatcctgggtaacaataatcggccctcgggggtccctgaccgactctccggctccacgtccggcacctcagcctccctggccatcactgggctccaggctgaggatgagggtacttattactgccagtcctatgacagcagcctgagtggttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 153]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtacagctgcagcagtcaggtccaggactggtgaagccctcgcagaccctctcactcacctgtggcatctccggggacagtgtctctaccaacagtgttgcttggcactggatcaggcagtccccatcgagaggccttgagtggctgggaaggacatactacaggtccaagtggtctaatgactatggagtatctgtgaaaagtcgaatcaccatcatcccagacacatccaagaaccagttctccctgcagctgaactctgtgactcccgaggacacggctgtgtattactgtgcgcgctcttcttcttggtaccagatcttcgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 154]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSGAPGQTVTISCTGGSSNIGTGYFVNWYQQVPGKAPKLLILGNNNRPSGVPDRLSGSTSGTSASLAITGLQAEDEGTYYCQSYDSSLSGYVFGTGTKVTV LG [SEQ ID NO:155] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQSGPGLVKPSQTLSLTCGISGDSVSTNSVAWHWIRQSPSRGLEWLGRTYYRSKWSNDYGVSVKSRITIIPDTSKNQFSLQLNSVTPEDTAVYYCARSSS WYQIFDYWGQGTLVTVSS[SEQ ID NO: 156] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 40 ET200-043 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagcgacagcatagccaacaactatgttcagtggtaccagcagcgcccgggcagtgcccccaccaatgtgatctacgaagatgtccaaagaccctctggggtccctgatcggttctctgggtccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgtctactattgtcagtcttatcatagcgacaatcgttgggtgttcggcggcgggaccaagctgaccgtcctaggt[SEQ ID NO: 157]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtggagtctgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtggtggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagccgaggacacggccgtatattactgtgcgcgctctggtgcttactgggactactctgtttacgatgaatggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 158]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTGSSDSIANNYVQWYQQRPGSAPTNVIYEDVQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEAVYYCQSYHSDNRWVFGGGTKLTV LG [SEQ ID NO:159] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSGAY WDYSVYDEWGQGTLVTVSS[SEQ ID NO: 160] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 41 ET200-044 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgactcagccaccctcagtgtccgtgtccccaggacagacagccaccatcgcctgttctggacataaattgggggataaatatgcttcctggtatcagcagaagtcgggccagtcccctgtgttgatcatctatcaggataataagcggccctcagggattcctgagcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctctggatgaggctgactattattgtcaggcgtgggacagtagtacttatgtggcattcggcggagggaccaagctgaccgtcctaggt [SEQID NO: 161]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctgcaggagtccggcccaggactggtgaagccttcggagaccctgtccctcacctgcgttgtctctggtggctccatcagcagtagtaactggtggagctgggtccgccagcccccagggaaggggctggagtggattggggaaatctatcatagtgggagccccaactacaacccatccctcaagagtcgagtcaccatatcagtagacaagtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcatgactactcatactttcggttacgatgcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 162]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSVSPGQTATIACSGHKLGDKYASWYQQKSGQSPVLIIYQDNKRPSGIPERFSGSNSGNTATLTISGTQALDEADYYCQAWDSSTYVAFGGGTKLTVLG [SEQ ID NO: 163]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQESGPGLVKPSETLSLTCVVSGGSISSSNWWSWVRQPPGKGLEWIGEIYHSGSPNYNPSLKSRVTISVDKSKNQFSLKLSSVTAADTAVYYCARMTTHTF GYDAWGQGTLVTVSS[SEQ ID NO: 164] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 42 ET200-045 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagcctgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccacgattacttgtgggggaaacaacattggaagtgaaagtgtgcactggtaccaccagaagccaggccaggcccctgtgttggtcatctatgatgatgccggccggccctcagggatccctgagcgattcactggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggacagaaatagtgctcagtttgtcttcggacctgggaccaaggtcaccgtcctaggt[SEQ ID NO: 165]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcggtgttcatctggattggtggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 166]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QPVLTQPPSVSVAPGKTATITCGGNNIGSESVHWYHQKPGQAPVLVIYDDAGRPSGIPERFTGSNSGNTATLTISRVEAGDEADYYCQVWDRNSAQFVFGPGTKVTVLG [SEQ ID NO: 167]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGVH LDWWGQGTLVTVSS [SEQID NO: 168] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 43 ET200-069 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtggttatgtcttcggaactgggaccaagctgaccgtcctaggt[SEQ ID NO: 169]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcctgtacgaaggtggttaccatggttggggttcttggctgtcttctgattcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO:170] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGYVFGTGTKLTVL G [SEQ ID NO:171] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLYEGGYHGWGSWLSSDSWGQGTLVTVSS [SEQ ID NO: 172] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 44 ET200-078 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttattgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 173]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgcgcgaaggggcatttgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 174]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYWVFGGGTKLTV LG [SEQ ID NO:175] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGAFDAFDIWG QGTMVTVS [SEQ IDNO: 176] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 45 ET200-079 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgagctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcttcatctataggaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtggttatctcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 177]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaatggcgactccaactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 178]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYELTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLFIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGYLFGTGTKVTVL G [SEQ ID NO:179] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCANGDSN YYYGMDVWGQGTTVTVSS[SEQ ID NO: 180] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 46 ET200-081 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgccctgactcagcctgcctccgtgtccgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacattggtggttataactatgtctcctggtaccaacaacacccaggcaaagcccccaaactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcatctcatatacacgcacctggaacccctatgtcttcgggagtgggaccaaggtcaccgtcctaggt[SEQ ID NO: 181]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtgcagtctgggggaggcgtggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccgtcaagctccagggaagggtctggagtgggtctctcttattagtggggatggtggtagcacatactatgcagactctgtgaagggccgattcaccatctccagagacaacagcaaaaactccctgtatctgcaaatgaacagtctgagaactgaggacaccgccttgtattactgtgcaaaagatcgggcagcagctggctactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 182]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSALTQPASVSGSPGQSITISCTGTSSDIGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCISYTRTWNPYVFGSGTKVTV LG [SEQ ID NO:183] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGGGVVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSLISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRTEDTALYYCAKDRAAAGYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 184] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 47 ET200-097 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)ctgcctgtgctgactcagccaccctcagtgtccgtgtccccaggacagacagccatcatcacctgctctggagataaattgggggaaaaatatgtttcctggtatcagcagaagccaggccagtcccctgtactggtcatcgatcaagataccaggaggccctcagggatccctgagcgattctctggctccaactctgggaccacagccactctgaccatcagcgggacccaggctatggatgaggctgactattactgtcaggcgtgggacaggggtgtggtattcggcggagggaccaagctgaccgtcctaggt [SEQ IDNO: 185]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggagacttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttaatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggagtggtaataacataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagatagtatacggtatggcatcacctggggaggttttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 186]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) LPVLTQPPSVSVSPGQTAIITCSGDKLGEKYVSWYQQKPGQSPVLVIDQDTRRPSGIPERFSGSNSGTTATLTISGTQAMDEADYYCQAWDRGVVFGGGTKLTVLG [SEQ ID NO: 187]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGDLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSGISWSGNNIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDSIRYGITWGGFDYWGQGTLVTVSS [SEQ ID NO: 188] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 48 ET200-098 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagcctgtgctgactcagccaccctcggtgtccaagggcttgagacagaccgccacactcacctgcactgggaacagcaacaatgttggcaacctaggagtagcttggctgcagcagcaccagggccaccctcccaaactcctatcctacaggaataacaaccggccctcagggatctcagagagattatctgcatccaggtcaggaaacacagcctccctgaccattactggactccagcctgaggacgaggctgactattactgctcagcatgggacagtagcctcagtgcttgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 189]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggagtcgtggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccgtcaagctccggggaagggtctggagtgggtctctcttattaattgggatggtggtagcacctactatgcagactctgtgaagggtcgattcaccatctccagagacaacagcaaaaactccctgtatctgcaaatgaacagtctgagagctgaggacaccgccttgtattactgtgcaaaagggatgggcctgagggcgtttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 190]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QPVLTQPPSVSKGLRQTATLTCTGNSNNVGNLGVAWLQQHQGHPPKLLSYRNNNRPSGISERLSASRSGNTASLTITGLQPEDEADYYCSAWDSSLSAWVFGGGTKLT VLG [SEQ ID NO:191] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGVVVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSLINWDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTALYYCAKGMG LRAFDYWGQGTLVTVSS[SEQ ID NO: 192] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 49 ET200-099 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcctgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtccggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcttcatgggatgacagcctgaatggccgttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 193]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtccagctggtacagtctggggctgaggtgaggaagcctggggcctcagtgaaggtttcctgcaagacttctggatacaccttcagttggtatgctatacattgggtgcgccaggcccccggacaaaggcttgagtggatgggatggatcaacgctggcaatggaaacacaaaatattcacagaaatttcagggcagagtcagtcttaccagggacacatccgcgagcacagcctacatggagctgagcagcctgagatctgatgacacggctgtgtattactgtgcgagacccgataattatggttcgggtggggatgtttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 194]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCASWDDSLNGRYVFGTGTKVTV LG [SEQ ID NO:195] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVRKPGASVKVSCKTSGYTFSWYAIHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVSLTRDTSASTAYMELSSLRSDDTAVYYCARPDNYGSGGDVFDIWGQGTMVTVSS [SEQ ID NO: 196] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 50 ET200-100 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactttgtgcagtggtaccagcagcgcccgggcagtgcccccacccctatgatctatgaggataacaacagaccccctggggtccctgatcggttctctgcctccgtcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgataccagcaatgtggtattcggcggggggaccaagctgaccgtcctaggt[SEQ ID NO: 197]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggaggcttggtacagcctggagggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatgaaatgaactgggtccgccaggctccagggaaggggctggagtgggtttcatacattagtagtagtggtagtaccatatactacgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggctgtttattactgtgcacgctgggactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 198]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTRSSGSIASNFVQWYQQRPGSAPTPMIYEDNNRPPGVPDRFSASVDSSSNSASLTISGLKTEDEADYYCQSYDTSNVVFGGGTKLTVLG [SEQ ID NO: 199]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARWDYG MDVWGQGTTVTVSS [SEQID NO: 200] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 51 ET200-101 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagccaccctcagcgtctggggcccccgggcagagggtcaccgtctcttgttctggaagcaactccaacatcggaagtaactacgttaactggtaccagcagttcccaggaacggcccccaaactcctcatgtatagtagtagtcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccactctgaggatgaggctgattattactgtgctacatgggatgacagcctgaatgcttgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 201]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggggctgaggtgaggaagcctggggcctcagtgaaggtttcctgcaagacttctggatacaccttcacttggtatgctatacattgggtgcgccaggcccccggacaaaggcttgagtggatgggatggatcaacgctggcagtggaaacacaaaatattcacagaaatttcagggcagagtcacccttaccagggacacatccgcgagcacagcgtacatggagctgagcagcctgagatctgatgacacggctgtgtattactgtgcgagacccaataactatggttcgggtggggatgtttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 202]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSASGAPGQRVTVSCSGSNSNIGSNYVNWYQQFPGTAPKLLMYSSSQRPSGVPDRFSGSKSGTSASLAISGLHSEDEADYYCATWDDSLNAWVFGGGTKLT VLG [SEQ ID NO:203] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVRKPGASVKVSCKTSGYTFTWYAIHWVRQAPGQRLEWMGWINAGSGNTKYSQKFQGRVTLTRDTSASTAYMELSSLRSDDTAVYYCARPNNYGSGGDVFDIWGQGTMVTVSS [SEQ ID NO: 204] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 52 ET200-102 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgagtgcttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 205]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtccagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaagtttcctgcaaggcttctggatacaccttcacgaactatgctctgcattgggtgcgccaggcccccggacaagggcttgagtggatggcatggatcaacggtggcaatggtaacacaaaatattcacagaacttccagggcagagtcaccattaccagggacacatccgcgagcacagcctatatggagctgagcagcctgagatctgaagacacggctgtgtattactgtgcgaaaccggaggaaacagctggaacaatccactttgactactggggccagggaaccccggtcaccgtctcctca [SEQ ID NO: 206]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAYVFGTGTKVTVL G [SEQ ID NO:207] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYALHWVRQAPGQGLEWMAWINGGNGNTKYSQNFQGRVTITRDTSASTAYMELSSLRSEDTAVYYCAKPEETAGTIHFDYWGQGTPVTVSS [SEQ ID NO: 208] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 53 ET200-103 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag +  HA tag)caggctgtgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcaccatcacggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 209]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtccagctggtacagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgggggagggttactatgatagtagtggttattccaacggtgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ IDNO: 210] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTITVFGGGTKLTVLG [SEQ ID NO: 211]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAGEGYYDSSGYSNGDAFDIWGQGTMVTVSS [SEQ ID NO: 212] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 54 ET200-104 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaatgtggtattcggcggagggaccaaggtcaccgtcctaggt[SEQ ID NO: 213]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggaggcttggtacagcctggagggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatgaaatgaactgggtccgccaggctccagggaaggggctggagtgggtttcatacattagtagtagtggtagtaccatatactacgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggctgtttattactgtgcacgctgggactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 214]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNVVFGGGTKVTVLG [SEQ ID NO: 215]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARWDYG MDVWGQGTTVTVSS [SEQID NO: 216] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 55 ET200-105 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgtgctgactcagccaccctcagtgtccgtgtccccaggacagacagccagcatcacctgctctggagatagattgacgaataaatatgtttcctggtatcaacagaagccaggccagtcccctgtgttggtcatctatgaggatgccaagcggccctcagggatccctgcgcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctatggatgagtctgaatattactgtcaggcgtgggacagcagtgtggtggtttttggcggagggaccaagctgaccgtcctaggt [SEQID NO: 217]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggatttacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagtataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagatgaggacacggccttgtattactgtgcaaaagaccgaggggggggagttatcgttaaggatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 218]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYVLTQPPSVSVSPGQTASITCSGDRLTNKYVSWYQQKPGQSPVLVIYEDAKRPSGIPARFSGSNSGNTATLTISGTQAMDESEYYCQAWDSSVVVFGGGTKLTVLG [SEQ ID NO: 219]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTALYYCAKDRGGGVIVKDAFDIWGQGTMVTVSS [SEQ ID NO: 220] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 56 ET200-106 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgagctgactcagccacccgcagcgtctgggacccccggacagagagtcaccatctcttgttctgggggcgtctccaacatcgggagtggtgctctaaattggtaccagcaactcccaggaacggcccccaaactcctcatctatagttacaatcagcggccctcaggggtctctgaccgattctctggctccaggtctgccacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcaacctgggatgatagtgtgaatggttgggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 221]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctggagctgaggtgaagaagcctggggattcagtgaaggtctcctgcaagccttctggttacaattttctcaactatggtatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggattagcacttacaccggtaacacaaactatgcacagaagctgcagggcagagtcaccttcaccacagacacatccacgagcacagcctacatggagatgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgccagcagggtggtggttggtacgatgtttggggtcaaggtactctggtcaccgtctcctca [SEQ ID NO: 222]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYELTQPPAASGTPGQRVTISCSGGVSNIGSGALNWYQQLPGTAPKLLIYSYNQRPSGVSDRFSGSRSATSASLAISGLQSEDEADYYCATWDDSVNGWVFGGGTKLTV LG [SEQ ID NO:223] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGAEVKKPGDSVKVSCKPSGYNFLNYGINWVRQAPGQGLEWMGWISTYTGNTNYAQKLQGRVTFTTDTSTSTAYMEMRSLRSDDTAVYYCARQQ GGGWYDVWGQGTLVTVSS[SEQ ID NO: 224] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 57 ET200-107 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggagagaaggtcaccatctcctgctctggaagcaacttcaatgttggaaataatgatgtatcctggtatcagcaactcccaggtgcagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctggacatcaccgggctccacagtgacgacgaggccgattattactgcggaacatgggatagcagcctgaatactgggggggtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 225]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatactatcagctgggtacgacaggcccctggacaagggcttgagtggatgggatggatcagcacttacaatggtctcacaaactatgcacagaacctccagggcagagtcaccatgactacagacacattcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattactgtgtgagagaggggtcccccgactacggtgacttcgcgtcctttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 226]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSAAPGEKVTISCSGSNFNVGNNDVSWYQQLPGAAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLDITGLHSDDEADYYCGTWDSSLNTGGVFGTGTKVT VLG [SEQ ID NO:227] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTISWVRQAPGQGLEWMGWISTYNGLTNYAQNLQGRVTMTTDTFTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFASFDYWGQGTLVTVSS [SEQ ID NO: 228] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 58 ET200-108 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctgcgcccccgggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagttcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggatttctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcgccggactccagactggggacgaggccgattattactgcggaacatgggataccagcctgagtggtttttatgtcttcggaagtgggaccaaggtcaccgtcctaggt[SEQ ID NO: 229]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatactatcagctgggtacgacaggcccctggacaagggcttgagtggatgggatggatcagcacttacaatggtctcacaaactatgcacagaacctccagggcagagtcaccatgactacagacacattcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattactgtgtgagagaggggtcccccgactacggtgacttcgcgtcctttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 230]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSAPPGQKVTISCSGSSSNIGNNYVSWYQQFPGTAPKLLIYDNNKRPSGISDRFSGSKSGTSATLGIAGLQTGDEADYYCGTWDTSLSGFYVFGSGTKVTVL G [SEQ ID NO:231] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTISWVRQAPGQGLEWMGWISTYNGLTNYAQNLQGRVTMTTDTFTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFASFDYWGQGTLVTVSS [SEQ ID NO: 232] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 59 ET200-109 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)ctgcctgtgctgactcagccaccctcagcgtctgcgacccccgggcagagggtcaccatctcttgttctggaaccacctccaacatcggaagtaatactgtacactggtaccagcagctcccagggacggcccccaaactcctcatctataataataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctacatattcctgtgcaacatgggatgacagcctgagtggtgtggtcttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 233]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagagatcccgcctacggtgactacgagtatgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 234]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) LPVLTQPPSASATPGQRVTISCSGTTSNIGSNTVHWYQQLPGTAPKLLIYNNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEATYSCATWDDSLSGVVFGGGTKLTVLG [SEQ ID NO: 235]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDPAYGDYEYDAFDIWGQGTMVTVSS [SEQ ID NO: 236] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

TABLE 60 ET200-110 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaactaatggtgtaaactggttccagcagttcccaggaacggcccccaaactcctcatctatactaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgcggatgaggctgattattactgtgcagtgtgggaccacagcctgaatggtccggtgttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 237]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagaggggccggttttgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 238]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSASGTPGQRVTISCSGSSSNIGTNGVNWFQQFPGTAPKLLIYTNDQRPSGVPDRFSGSKSGTSASLAISGLQSADEADYYCAVWDHSLNGPVFGGGTKLTVL G [SEQ ID NO:239] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGAGFD AFDIWGQGTMVTVSS[SEQ ID NO: 240] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 61 ET200-111 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgagactgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 241]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagaggggctagatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 242]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDETDYYCAAWDDSLNGYVFGTGTKVTVL G [SEQ ID NO:243] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGLDAFD IWGQGTMVTVSS [SEQID NO: 244] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 62 ET200-112 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatgtatagtaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattattgtgcagcatgggatgacagcctgaatggttatgtcttcgcagctgggacccagctcaccgttttaagt[SEQ ID NO: 245]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagaggggctagatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 246]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLMYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFAAGTQLTV LS [SEQ ID NO:247] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGLDAFD IWGQGTMVTVSS [SEQID NO: 248] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 63 ET200-113 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcactggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgagtgctgcttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 249]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacagctttaccagctatactatcagctgggttcgacaggcccctggacaaggccttgagtggatgggatgggtcagcacttacaatggtctcagaaactatgcacagaacctccagggcagagtcaccatgactacagacacactcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattattgtgtgagagaggggtcccccgactacggtgacttcgcggcctttgactactggggccagggcaccctggtcaccgtctcctca [SEQ ID NO: 250]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAAYVFGTGTKVTV LG [SEQ ID NO:251] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKASGYSFTSYTISWVRQAPGQGLEWMGWVSTYNGLRNYAQNLQGRVTMTTDTLTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFAAFDYWGQGTLVTVSS [SEQ ID NO: 252] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 64 ET200-114 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagccaccctcagcgtctgagacccccgggcagagggtcaccatctcttgttctggaagcaggtccaacatcggaactaatattgtacactggtaccagcagcgcccaggaatggcccccaaactcctcacttatggtagtcggcggccctcaggggtcccggaccgattctctggctccaagtttggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattattgtgcagcatgggatgacagtctgaatggtccggctttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 253]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagacggtgggggctactttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 254]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSASETPGQRVTISCSGSRSNIGTNIVHWYQQRPGMAPKLLTYGSRRPSGVPDRFSGSKFGTSASLAISGLQSEDEADYYCAAWDDSLNGPAFGGGTKLTVL G [SEQ ID NO:255] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGGGYF DYWGQGTLVTVSS [SEQID NO: 256] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 65 ET200-115 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaatatcggggcacgttatgatgtacactggtaccagcaactcccaggaacagccccccgactcctcatctctgctaactacgatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagtgtgagtgcttgggtgttcggcggagggaccaaggtcaccgtcctaggt[SEQ ID NO: 257]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaagtgcagctggtgcagtctggggctgaagtgaaggagcctggggcctcagtgaggatctcctgccaggcatctggatacaacttcatcagttattatatgcactgggtgcggcaggcccctgggcaaggtcttgagtggatgggcaccatcaacccaggcagtggtgagacagactactcacagaagttgcagggcagagtcaccatgaccagggacccgtccacgggtacattcgacatggggctgagcagcctgacatctggggacacggccgtctattattgtgcgacaggtctcatcagaggagctagcgatgcttttaatatctggggccgggggacaatggtcaccgtctcttca [SEQ ID NO: 258]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSGAPGQRVTISCTGSSSNIGARYDVHWYQQLPGTAPRLLISANYDRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSVSAWVFGGGTKVT VLG [SEQ ID NO:259] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKEPGASVRISCQASGYNFISYYMHWVRQAPGQGLEWMGTINPGSGETDYSQKLQGRVTMTRDPSTGTFDMGLSSLTSGDTAVYYCATGLIR GASDAFNIWGRGTMVTVSS[SEQ ID NO: 260] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 66 ET200-116 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagcctgtgctgactcagccaccctcagtgtccgtgtccccaggacagacggccgccatcccctgttctggagataagttgggggataaatttgcttcctggtatcagcagaagccaggccagtcccctgtgctggtcatctatcaagatactaagcggccctcagggatccctgagcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctatggatgaggctgactattactgtcagacgtgggccagcggcattgtggtgttcggcggagggaccaagctgaccgtcctaggt [SEQID NO: 261]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtacagctgcagcagtcaggtccaggactggtgaagccctcgcagaccctctcactcacctgtgccatctccggggacagtgtctctagcaacagtgctgcttggaactggatcaggcagtccccatcgagaggccttgagtggctgggaaggacatactacaggtccaagtggtataatgattatgcagtatctgtgaaaagtcgaataaccatcaacccagacacatccaagaaccagttctccctgcagctgaactctgtgactcccgaggacacggctgtgtattactgtgcaagagagcgcagtggctggaagggatttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 262]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QPVLTQPPSVSVSPGQTAAIPCSGDKLGDKFASWYQQKPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQTWASGIVVFGGGTKLTVLG [SEQ ID NO: 263]SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCARERS GWKGFDYWGQGTLVTVSS[SEQ ID NO: 264] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 67 ET200-117 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)gatgttgtgatgactcagtctccaccctccctgtccgtcacccctggagagccggcctccatcacctgcaggtctagtcagagcctcctggaaagaaatgcatacaactacttggattggtacctgcagaggccaggacagtctccacagctcctgatctacttgggttctaatcgggccgccggggtccctgacaggttcagtggcagtggatcaggcagagattttacactgaaaatcagcagagtggagcctgaggatgttggggtttattactgcatgcaagctctacaagctccgttcactttcggcggagggaccaaggtggagatcaaacgt[SEQ ID NO: 265]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaagtgcagctggtgcagtctgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtggtggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagccgaggacacggccgtatattactgtgcgaaatggggcccgtttcaggatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 266]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) DVVMTQSPPSLSVTPGEPASITCRSSQSLLERNAYNYLDWYLQRPGQSPQLLIYLGSNRAAGVPDRFSGSGSGRDFTLKISRVEPEDVGVYYCMQALQAPFTFGGGTKV EIKR [SEQ ID NO:267] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKWGPF QDAFDIWGQGTMVTVSS[SEQ ID NO: 268] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 68 ET200-118 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactatgtctcctggtaccaacagcacccgggcaaagcccccaaactcatgatttatgaggtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcaccccttatgtcttcggagcagggaccaaggtcaccgtcctaggt[SEQ ID NO: 269]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagccaggtggacagcagtggcatcagaccaccactttgactactggggccagggaacgctggtcaccgtctcctca [SEQ ID NO: 270]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTPYVFGAGTKVTV LG [SEQ ID NO:271] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKARWTAVASDHHFDYWGQGTLVTVSS [SEQ ID NO: 272] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 69 ET200-119 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgcttactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaagctgaccgtcctaggt[SEQ ID NO: 273]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagagattgggactacatggacgtctggggcaaagggaccacggtcaccgtctcctca [SEQ ID NO: 274]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKLTVL G [SEQ ID NO:275] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDWDYM DVWGKGTTVTVSS [SEQID NO: 276] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 70 ET200-120 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgagctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 277]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtgcagctggtggagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgagagacctatctcggggagctaacccgcattactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQID NO: 278] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYELTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVL G [SEQ ID NO:279] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDLSRGANPHYYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 280] TSGQAGQHHHHHHGAYPYDVPDYAS[SEQ ID NO: 308]

TABLE 71 ET200-121 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccgtctcctgcactgggagcagatccaacatcggggcaggatatgatgtacactggtaccagcaacttccaggaacagcccccaaactcctcatctatggaaatagtaatcggcctccaggggtccctgaccgattctctgggtctaagtctggcacctcagcctccctggtcatcactgggctccaggctgaggatgccgctgattattactgccagtcctatgacaacactgtgcgtgaatcaccttatgtcttcggaactgggaccaaggtcaccgtcctaggt [SEQ ID NO: 281]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtacagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcaacagagagtaatttagtgtcccggcactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO:282] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QSVLTQPPSVSGAPGQRVTVSCTGSRSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPPGVPDRFSGSKSGTSASLVITGLQAEDAADYYCQSYDNTVRESPYVFGTGTK VTVLG [SEQ IDNO: 283] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATESNLVSRHYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 284] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQID NO: 308]

TABLE 72 ET200-122 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)ctgcctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaaccagctccaacatcggaagtaattctgtagactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgaatctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 285]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaagtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggatacaccttcaccggctactatatgcactgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcaaccctaacagtggtggcacaaactatgcacagaagtttcagggcagggtcaccatgaccagggacacgtccatcagcacagcctacatggagctgagcaggctgagatctgacgacacggccgtgtattactgtgcgagagattacggatactatggttcggggagttattcgagcggccccctttactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca[SEQ ID NO: 286] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) LPVLTQPPSASGTPGQRVTISCSGTSSNIGSNSVDWYQQLPGTAPKLLIYSNNQRPSGVPDRISGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVL G [SEQ ID NO:287] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYGYYGSGSYSSGPLYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 288]TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 73 ET200-123 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)caggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatgtataataatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctcaatggttatgtcttcggacctgggaccaaggtcaccgtcctaggt[SEQ ID NO: 289]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtggagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgagagacctatctcggggagctaacccgcattactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQID NO: 290] ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLMYNNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGPGTKVT VLG [SEQ ID NO:291] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDLSRGANPHYYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 292] TSGQAGQHHHHHHGAYPYDVPDYAS[SEQ ID NO: 308]

TABLE 74 ET200-125 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)aattttatgctgactcagccccacgctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagtattgccagcaactatgtgcagtggtaccagcagcgcccgggcagttccccccgcactgtgatttatgaggataatcaaagaccctctggggtccctggtcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgattccaccagtgtgcttttcggcggagggaccaagctgaccgtcctaggt[SEQ ID NO: 293]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]gaggtccagctggtgcagtctggggctgaggtgaagaagccagggtcctcggtgaaggtctcctgcaaggcctcgggaggcaccttcagcagcaattctctcagctgggtgcgacaggcccctggacaagggcttgagtggatgggaaggatcttccctatcctgggtataacaaactatgcacagaagttccagggcagagtcacgattaccgcggacaaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtctattactgtgcgagaggaaactaccaatggtatgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 294]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) NFMLTQPHAVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPRTVIYEDNQRPSGVPGRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTSVLFGGGTKLTVLG [SEQ ID NO:295] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSNSLSWVRQAPGQGLEWMGRIFPILGITNYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARGNYQW YDAFDIWGQGTMVTVSS[SEQ ID NO: 296] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 75 ET200-005 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)cagcctgtgctgactcagccaccctcagtgtcagtggtcccaggaaagacggccaggattacctgtgggggaaaaaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtggtggtcatccattatgatagtgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 297]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccaactatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacataagctccagggcagagtcaccatgaccacagacacatccacgagcacagccaacatggagctgaggagcctgagacctgacgacactgccgtgtattactgtgcgcgctcttacttcggttctcatgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 298]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) QPVLTQPPSVSVVPGKTARITCGGKNIGSKSVHWYQQKPGQAPVVVIHYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVL G [SEQ ID NO:299] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGISWVRQAPGQGLEWMGWISAYNGNTNYAHKLQGRVTMTTDTSTSTANMELRSLRPDDTAVYYCARSY FGSHDYWGQGTLVTVSS[SEQ ID NO: 300] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 308]

TABLE 76 ET200-124 DNA Sequence (light chain variable region scFv linkerheavy chain variable region His tag + HA tag)tcctatgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggatttcctgtgggggaaacgacattggaagtaaaagtgttttctggtatcagcagaggccaggccaggcccctgtgttggtcgtctatgatgatagcgaccggccctcagggctccctgagcgattctctggcttcaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaagtgtgggatagtagtagtgatcattatgtcttcggaactgggaccaaggtcaccgtcctaggt[SEQ ID NO: 301]tctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcc [SEQ IDNO: 305]caggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagatataacctatggttcggggagttatggtgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 302]ACTAGTGGCCAGGCCGGCCAGCACCATCACCATCACCATGGCGCATACCCGTACGACGTTCCGGACTACGCTTCT [SEQ ID NO: 306] Amino Acid Sequence (lightchain variable region scFv linker heavy chain variable region His tag+ HA tag) SYVLTQPPSVSVAPGKTARISCGGNDIGSKSVFWYQQRPGQAPVLVVYDDSDRPSGLPERFSGFNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKVTVL G [SEQ ID NO:303] SRGGGGSGGGGSGGGGSLEMA [SEQ ID NO: 307]QVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDITYGSGSYGAFDIWGQGTMVTVSS [SEQ ID NO: 304] TSGQAGQHHHHHHGAYPYDVPDYAS [SEQ IDNO: 308]

XI. Exemplary Extracellular Antigen-Binding Domains (e.g., scFvs)Comprising a Heavy Chain Variable Region, a Light Chain Variable Regionand a Linker Peptide

TABLE 77 ET200-001 DNA SequenceCagtctgtgttgacgcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtgtatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcgaaggtccgtacgacggtttcgattcttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 593] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGPYDGFDSWGQGTLVTVSS [SEQ ID NO: 594]

TABLE 78 ET200-002 DNA SequenceAattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattctgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggcactgaggtgaagaagcctggggcctcagtgagggtcgcctgcaaggcttctggttacccctttaacaaatatgacatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggaggcatcatccctatctttcgtacaacaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtatattactgtgcgcgcgaatggttctactgggatatctggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 595] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNSVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGTEVKKPGASVRVACKASGYPFNKYDINWVRQAPGQGLEWMGGIIPIFRTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREWFYWDIWGQGTLVTVSS [SEQ ID NO: 596]

TABLE 79 ET200-003 DNA SequenceCagtctgtgttgactcagccaccctcagtgtccgtgtccccaggacagacagccagcatctcctgctctggaaataaattggggactaagtatgtttactggtatcagaagaggccaggccagtcccctgtgttggtcatgtatgaagataatcagcggccctcagggatcccggagcggttctctggctccaactctgggaacacagccactctgaccatcagagggacccagactgtggatgaggctgactattactgtcaggcgtgggactccgacactttcgtggtcttcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagaccgggggaggcgtggtccagcctgggaggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatggcatgcactgggtccgccaggctccaggcaaggggctggagtgggtggcagttatatcacatgatggaagtaataaatactacgcagactccgtgaagggccgattcaccatctccagagacaattccaaggacacgctgtatctgcaaatgaacagcctgagaggtgaggacacggccgtatattactgtgcgcgctctaaccagtggtctggttacttctctttcgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 597] Amino Acid SequenceQSVLTQPPSVSVSPGQTASISCSGNKLGTKYVYWYQKRPGQSPVLVMYEDNQRPSGIPERFSGSNSGNTATLTIRGTQTVDEADYYCQAWDSDTFVVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISHDGSNKYYADSVKGRFTISRDNSKDTLYLQMNSLRGEDTAVYYCARSNQWSGYFSFDYWGQGTLVTVSS [SEQ ID NO: 598]

TABLE 80 ET200-006 DNA SequenceTcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtggtggtcatccattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccacctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcaacacttacaatggtcacacaaactatgcacagaagctccagggcagagccacaatgaccgcagacacatccacgaacacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgcgttatctacggttctggtgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 599] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVVVIHYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGISWVRQAPGQGLEWMGWINTYNGHTNYAQKLQGRATMTADTSTNTAYMELRSLRSDDTAVYYCARVIYGSGDYWGQGTLVTVSS [SEQ ID NO: 600]

TABLE 81 ET200-007 DNA SequenceTcctatgtgctgactcagccactctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaactgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatcgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctgcaggagtcgggcccaggactggtgaagccttcggagaccctgtccctcacctgcaatgtctctggttactccatcagcagtggttacttttggggctggatccggcagcccccagggaaggggctggagtggattgggagtatctatcatagtaggagcacctactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgaactctgtgaccgccgcagacacggccgtgtattactgtgcgcgcggttacggttacttcgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 601] Amino Acid SequenceSYVLTQPLSVSVAPGKTARITCGGNNIGSKTVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHRVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQESGPGLVKPSETLSLTCNVSGYSISSGYFWGWIRQPPGKGLEWIGSIYHSRSTYYNPSLKSRVTISVDTSKNQFSLKLNSVTAADTAVYYCARGYGYFDYWGQGTLVTVSS [SEQ ID NO: 602]

TABLE 82 ET200-008 DNA SequenceCaatctgccctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactatgtctcctggtaccaacaacacccaggcaaagcccccaaactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcacttcgaaggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggtgtggtacggcctggggggtccctgagactctcctgtgcagcctctggattcacctttggtgattatggcatgagctgggtccgccaagctccagggaaggggctggagtgggtctctggtattaattggaatggtggtagcacaggttatgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagccgaggacacggccgtatattactgtgcgcgctctaaatacaacttccatgtttactacgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 603] Amino Acid SequenceQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTSKVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGVVRPGGSLRLSCAASGFTFGDYGMSWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSKYNFHVYYDYWGQGTLVTVSS [SEQ ID NO: 604]

TABLE 83 ET200-009 DNA SequenceCagtctgtgttgacgcagccaccctcagcgtctgggacccccgggcagacagtcaccatctcttgttctggaagcaactccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcctcatctataggaataatcagcggccctcaggggtccctgaccgattctcaggctccaagtctggcacctcagcctccctggccatcagtgggctccgctccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtgcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgctcttctggtaacatggtttcttggaaagatatgtggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 605] Amino Acid SequenceQSVLTQPPSASGTPGQTVTISCSGSNSNIGSNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARSSGNMVSWKDMWGQGTLVTVSS [SEQ ID NO: 606]

TABLE 84 ET200-010 DNA SequenceCaatctgccctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactctgtctcctggtaccaacaacacccaggcaaagcccccagactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcacccctttagtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcggtgctgttgcttaccatgattggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 607] Amino Acid SequenceQSALTQPASVSGSPGQSITISCTGTSSDVGGYNSVSWYQQHPGKAPRLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTPLVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGAVAYHDWGQGTLVTVSS [SEQ ID NO: 608]

TABLE 85 ET200-011 DNA SequenceCagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagagggtcaccatctcctgctctggaagcagctccaacatttcgatttatgatgtatcctggtatcagcagctcccaggaacagcccccaaactcctcatttatggcaataataagcgaccctcggggattgctgaccgattctctggctccacgtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatgacagtctgagtgggggggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcaatctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcgaggcttctggaggcaccctcagcagctatgctatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatgtttggtacagcacactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgaaaacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtgttcattacgcttctttcgatcattggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 609] Amino Acid SequenceQSVVTQPPSVSAAPGQRVTISCSGSSSNISIYDVSWYQQLPGTAPKLLIYGNNKRPSGIADRFSGSTSGTSATLGITGLQTGDEADYYCGTWDDSLSGGVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGSSVKVSCEASGGTLSSYAINWVRQAPGQGLEWMGGIIPMFGTAHYAQKFQGRVTITADESTKTAYMELSSLRSEDTAVYYCARGVHYASFDHWGQGTLVTVSS [SEQ ID NO: 610]

TABLE 86 ET200-012 DNA SequenceCagtctgtgttgacgcagccgccctcagtgtctgcggccgcaggacagaaggtcaccatctcctgctctggaagcgactccaacattgggaataattatgtgtcctggtatcaacacctcccagggacagcccccaaactcctcatttatgacgttaaaaatcgaccctcagggattcctgaccggttctccggctccaagtctggctcgtcagccaccctaggcatcgccggactccagcctggggacgaggccgattattactgcggaacatgggacagtcggctggatgcctatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcaatctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaagacttctggtttcccctttaatatctttggaatcacctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcggttacaacggtaacacagactacccacagaagttccagggcagagtcaccatgtccacagacacatccacgagtacagcctacatggagctgaggaacctgaaatctgacgacacggccgtgtattactgtgcgcgcggtgcttacggtggtatggatacttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 611] Amino Acid SequenceQSVLTQPPSVSAAAGQKVTISCSGSDSNIGNNYVSWYQHLPGTAPKLLIYDVKNRPSGIPDRFSGSKSGSSATLGIAGLQPGDEADYYCGTWDSRLDAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGASVKVSCKTSGFPFNIFGITWVRQAPGQGLEWMGWISGYNGNTDYPQKFQGRVTMSTDTSTSTAYMELRNLKSDDTAVYYCARGAYGGMDTWGQGTLVTVSS [SEQ ID NO: 612]

TABLE 87 ET200-013 DNA SequenceCagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcacctccaacatcggggcaggttatgatgtacactggtatcagcagcttccaggaacagcccccaaactcctcatctatactaacaactttcggccctcaggggtccctgaccgattctctgcctccaagtctggcacttcagcttccctggccatcactggtctccaggctgaggatgaggctgattattactgcggaacatgggatagcagcctgagtgccgttgtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctggaactgaggtgaagaagcctggggcctcagtgaaagtctcctgcaaggcttctggttacatgtttaccagttatggtctcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgctaacaatggtaagacaaattatgctaagaaattccaggacagagtcaccatgaccagagacacttccacgagcacaggctacatggaactgaggagcctgagatctgacgacacggccgtatattactgtgcgcgccatatcggtggttcttacttcgatcgttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 613] Amino Acid SequenceQSVVTQPPSVSGAPGQRVTISCTGSTSNIGAGYDVHWYQQLPGTAPKLLIYTNNFRPSGVPDRFSASKSGTSASLAITGLQAEDEADYYCGTWDSSLSAVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGTEVKKPGASVKVSCKASGYMFTSYGLNWVRQAPGQGLEWMGWISANNGKTNYAKKFQDRVTMTRDTSTSTGYMELRSLRSDDTAVYYCARHIGGSYFDRWGQGTLVTVSS [SEQ ID NO: 614]

TABLE 88 ET200-014 DNA SequenceTcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagactgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtgatggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagacgaggacacggccgtatattactgtgcgcgctctcatgaagctaacctggttggtgattggtggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 615] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSDGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSHEANLVGDWWGQGTLVTVSS [SEQ ID NO: 616]

TABLE 89 ET200-015 DNA SequenceCagtctgtggtgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctacggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgctggggtggtttcggtgctgttgatcattggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 617] Amino Acid SequenceQSVVTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARWGGFGAVDHWGQGTLVTVSS [SEQ ID NO: 618]

TABLE 90 ET200-016 DNA SequenceTcttctgagctgactcaggaccctgctgtgtctgtggccttgggacagacagtcaagatcacgtgccaaggagacagcctcacagactaccatgcaacctggtaccagcagaagccaggacaggcccctgtcgctgtcatctatgctacaaacaaccggcccactgggatcccagaccgattctctggttccagttccggaaacacagcttctttgaccatcactggggctcaggcggaagatgaggctgactattactgtaattcccgggacagcggcacggacgaagtgttattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagactgggggaggcctggtcaagcctggggggtccctgagactctcctgtgcagcctctggattcaccttcagtagctatagcatgaactgggtccgccaggctccagggaaggggctggagtgggtctcatccattagtagtagtagtagttacatatactacgcagactcagtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggccgtgtattactgtgcgcgcggtcagggttacgattactggggtcaaggtactctggtgaccgtctcctca [SEQID NO: 619] Amino Acid SequenceSSELTQDPAVSVALGQTVKITCQGDSLTDYHATWYQQKPGQAPVAVIYATNNRPTGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSGTDEVLFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGQGYDYWGQGTLVTVSS [SEQ ID NO: 620]

TABLE 91 ET200-017 DNA SequenceTcctatgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcgtctatgatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgagcatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatactgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgctactacccgggtatggatatgtggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 621] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLSISRVEAGDEADYYCQVWDSSSDHTVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARYYPGMDMWGQGTLVTVSS [SEQ ID NO: 622]

TABLE 92 ET200-018 DNA SequenceCaggctgtgctgactcagccgccctcaacgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcgggagaaatggtgtaaactggtaccagcagctcccaggagcggcccccaaagtcctcatctataatgataatcagcgaccctcaggggtccctgaccgagtctctggctcccagtctggctcctcaggcaccctggccatcgatgggcttcggtctgaggatgaggctgattattactgtgcggcatgggatgacagcctgcatggtgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcaatgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtggttacggtgattcttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 623] Amino Acid SequenceQAVLTQPPSTSGTPGQRVTISCSGSSSNIGRNGVNWYQQLPGAAPKVLIYNDNQRPSGVPDRVSGSQSGSSGTLAIDGLRSEDEADYYCAAWDDSLHGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKVSGYTLNELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARGGYGDSWGQGTLVTVSS [SEQ ID NO: 624]

TABLE 93 ET200-019 DNA SequenceAattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattcttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcaatctggggctgaggtgaagaggcctgggtcctcggtgaaggtctcctgcacggcttctggaggcaccttcagcagcgatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggaggaatcatccctatgtttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcgaaggttactactacccgtctgcttacctgggttctgttctgaacgacatctcttctgtttacgatgaatggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 625] Amino AcidSequence NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNSWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKRPGSSVKVSCTASGGTFSSDAISWVRQAPGQGLEWMGGIIPMFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYPSAYLGSVLNDISSVYDEWGQGTLVTVSS [SEQ ID NO: 626]

TABLE 94 ET200-020 DNA SequenceCagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcacctccaacattggaaataatgatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcgtgagtgcttcttgggtcttcggcagagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatccacagaagctccagggcagagtcaccatgaccacagacccatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgctctatgacttctttcgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 627] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSTSNIGNNDVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSVSASWVFGRGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYPQKLQGRVTMTTDPSTSTAYMELRSLRSDDTAVYYCARSMTSFDYWGQGTLVTVSS [SEQ ID NO: 628]

TABLE 95 ET200-021 DNA SequenceCagtctgtgttgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcaactccaacattgggaataattatgtatcctggtatcagcaactcccagggacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaggtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatggaataccactgtgactcctggctatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacaccgccatgtattactgtgcgcgctctgtttacgacctggatacttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 629] Amino Acid SequenceQSVLTQPPSVSAAPGQKVTISCSGSNSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSRSGTSATLGITGLQTGDEADYYCGTWNTTVTPGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAMYYCARSVYDLDTWGQGTLVTVSS [SEQ ID NO: 630]

TABLE 96 ET200-022 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgggggccccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtcttggggaggctcggaacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagcggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaattccctgtatctgcaaatgaacagtctgagagctgaggacaccgccatgtattactgtgcgcgctaccgtcaggttggttctgcttacgattcttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 631] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLGAPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSWGGSEQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAMYYCARYRQVGSAYDSWGQGTLVTVSS [SEQ ID NO: 632]

TABLE 97 ET200-023 DNA Sequencectgcctgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtatcagcagaagccaggccaggcccctgtgctggtcgtctatgctgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagttatcataattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgagcagcctgagatctgaggacaccgccatgtattactgtgcgcgctactggggtttcggtgtttctgatcgttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 633] Amino Acid SequenceLPVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYADSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSYHNYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELSSLRSEDTAMYYCARYWGFGVSDRWGQGTLVTVSS [SEQ ID NO: 634]

TABLE 98 ET200-024 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccccgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgacagcagcaatctttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctacaactactactactacgattcttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 635] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNLWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARYNYYYYDSWGQGTLVTVSS [SEQ ID NO: 636]

TABLE 99 ET200-025 DNA Sequencegacatccagatgacccagtctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagtcagagcattagcagctatttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctatgctgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttactactgtcaacagagttacagtaccccattcactttcggccctgggaccaaagtggatatcaaacgttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacaccgccatgtattactgtgcgcgctactggggttacgactcttacgatgaatggggtcaaggtactctggtgaccgtctcctca [SEQID NO: 637] Amino Acid SequenceDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIKRSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAMYYCARYWGYDSYDEWGQGTLVTVSS [SEQ ID NO: 638]

TABLE 100 ET200-026 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcaacaaccattactacaacgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 639] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARNNHYYNDYWGQGTLVTVSS [SEQ ID NO: 640]

TABLE 101 ET200-027 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagggggtcaccatcccctgcactgggagcagctccaacatcggggcaggttatgatgtacactggtaccagcagcttccagggacagcccccaaactcctcatctatggtaacaacaatcggccctcaggggtccctgaccgcttctctggctccaggtctggctcctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtgatgtggtattcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctggggctacagtgaaaatctcctgcaaggtttctggatacaccttcaccgactactacatgcactgggtgcaacaggcccctggaaaagggcttgagtggatgggacttgttgatcctgaagatggtgaaacaatatacgcagagaagttccagggcagagtcaccataaccgcggacacgtctacagacacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgctactggtcttactctttcgactacctgtacatgccggaaggtaacgattggtggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 641] Amino Acid SequenceQSVLTQPPSVSGAPGQGVTIPCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSRSGSSASLAITGLQAEDEADYYCQSYDSSLSDVVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGATVKISCKVSGYTFTDYYMHWVQQAPGKGLEWMGLVDPEDGETIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCARYWSYSFDYLYMPEGNDWWGQGTLVTVSS [SEQ ID NO: 642]

TABLE 102 ET200-028 DNA Sequencecagtctgtgttgactcagccacccgcagcgtctgggacccccggacagagagtcaccatctcttgttctgggggcgtctccaacatcgggagtggtgctctaaattggtaccagcaactcccaggaacggcccccaaactcctcatctatagttacaatcagcggccctcaggggtctctgaccgattctctggctccaggtctgccacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcaacctgggatgatagtgtgaatggttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggagctgaggtgaagaagcctggggattcagtgaaggtctcctgcaagccttctggttacaattttctcaactatggtatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggattagcacttacaccggtaacacaaactatgcacagaagctgcagggcagagtcaccttcaccacagacacatccacgagcacagcctacatggagatgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcgacctgtactactacgaaggtgttgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 643] Amino Acid SequenceQSVLTQPPAASGTPGQRVTISCSGGVSNIGSGALNWYQQLPGTAPKLLIYSYNQRPSGVSDRFSGSRSATSASLAISGLQSEDEADYYCATWDDSVNGWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGDSVKVSCKPSGYNFLNYGINWVRQAPGQGLEWMGWISTYTGNTNYAQKLQGRVTFTTDTSTSTAYMEMRSLRSDDTAVYYCARDLYYYEGVDYWGQGTLVTVSS [SEQ ID NO: 644]

TABLE 103 ET200-029 DNA Sequencecaggctgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccagggttacctgtgggggaaacaacattggaagtgaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgttggtcatctattatgataccgaccggccctcagggatccctgagcgattctctggctcccactctgggaccacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagggatcatgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctgggggaggcgtggtccagcctgggaggtccctgagactctcctgtgcggcctctggattcaccttcagtagctatgctatgcactgggtccgccaggctccaggcaagggactggagtgggtggcagttatatcatatgatggaagcaataaatactacgcagactccgtgaagggcctattcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagctgaggacacggccgtgtattactgtgcgcgctcttacttcacttctggtttctacgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 645] Amino Acid SequenceQAVLTQPPSVSVAPGKTARVTCGGNNIGSESVHWYQQKPGQAPVLVIYYDTDRPSGIPERFSGSHSGTTATLTISRVEAGDEADYYCQVWDSSRDHVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGLFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYFTSGFYDYWGQGTLVTVSS [SEQ ID NO: 646]

TABLE 104 ET200-030 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagttccaacatcggggcaggttatgatgtaaattggtatcagcagtttccaggaacagcccccaaactcctcatctatggtaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggctcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcatgtcttctatgtactacgattggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 647] Amino Acid SequenceQSVVTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVNWYQQFPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGSYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGASVKVSCKASGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARMSSMYYDWGQGTLVTVSS [SEQ ID NO: 648]

TABLE 105 ET200-031 DNA Sequencetcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagactgggggaggcttggtcaagcctggagggtccctgagactctcctgtgcagcctctggattcaccgtcagtgactactacatgagctggatccgccaggctccagggaagggcctggagtggatttcatacattagtggtagtggtaatagcatatactacgcagactctgtgaagggccgattcaccatctccagggacaacgccaagaactcactggatctgcaaatgaccagcctgagagccgaggacacggccgtatattactgtgcgcgctctactaaattcgattactggggtcaaggtactctggtgaccgtctcctca [SEQ IDNO: 649] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGLVKPGGSLRLSCAASGFTVSDYYMSWIRQAPGKGLEWISYISGSGNSIYYADSVKGRFTISRDNAKNSLDLQMTSLRAEDTAVYYCARSTKFDYWGQGTLVTVSS [SEQ ID NO: 650]

TABLE 106 ET200-032 DNA Sequencectgcctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacgtcggaagttacactgtaaactggtaccggcaactcccaggaacggcccccacactcctcatctataataataatcagcggccctcaggggtccctgaccgattctctgactccaagtctggcacctcggcctccctgaccattagtgggctccagcctgaggatgaggctgattattattgtgcagcatgggatgacaggctgggtggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggagcagaggtgaaaaagccgggggagtctctgaagatctcctgtaagggttctggatacagctttaccaactactggatcggctgggtgcgccagatgcccgggaaaggcctggagtggatggggatcatctatcctggtgactctgataccagatacagcccgtccttccaaggccaggtcaccatctcagccgacaagtccatcagcaccgcctacctacagtggagcagcctgaaggcctcggacaccgccatgtattactgtgcgcgctctactggttcttctcatatgtctgatgaatggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 651] Amino Acid SequenceLPVLTQPPSASGTPGQRVTISCSGSSSNVGSYTVNWYRQLPGTAPTLLIYNNNQRPSGVPDRFSDSKSGTSASLTISGLQPEDEADYYCAAWDDRLGGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARSTGSSHMSDEWGQGTLVTVSS [SEQ ID NO: 652]

TABLE 107 ET200-033 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaatcattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaagtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggagatcactcatagtggaaggtccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgctcttctatcatgtctgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 653] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNHWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEITHSGRSNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSSIMSDYWGQGTLVTVSS [SEQ ID NO: 654]

TABLE 108 ET200-034 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcacctccaacatcggggcaggttatgatgtacactggtaccagcagcttccaggaacagcccccaaactcctcatcaacaataacaggaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatggcagcctgactggtgcagtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcatgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcggttctgctctggaccattacgatcgttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 655] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSTSNIGAGYDVHWYQQLPGTAPKLLINNNRNRPSGVPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDGSLTGAVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSALDHYDRWGQGTLVTVSS [SEQ ID NO: 656]

TABLE 109 ET200-035 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcaccaattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctacaactactacttcaacgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 657] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTNWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARYNYYFNDYWGQGTLVTVSS [SEQ ID NO: 658]

TABLE 110 ET200-037 DNA Sequencetcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgctctatgttcggtgctcatgattcttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 659] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARSMFGAHDSWGQGTLVTVSS [SEQ ID NO: 660]

TABLE 111 ET200-038 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaacatcggggcaggttttgatgtacactggtaccagctacttccaggaacagcccccaaactcctcatctatgctaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctcctggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggtgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcaatctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtgcttctttcgaccgtcatgataactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 661] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGFDVHWYQLLPGTAPKLLIYANSNRPSGVPDRFSGSKSGTSASLAITGLLAEDEADYYCQSYDSSLSGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGASFDRHDNWGQGTLVTVSS [SEQ ID NO: 662]

TABLE 112 ET200-039 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagttcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgctctaactactactacaacgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 663] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSNYYYNDYWGQGTLVTVSS [SEQ ID NO: 664]

TABLE 113 ET200-040 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaacatcggggcaggttatgatgtacactggtaccagcagcttccaggaacagcccccaaactcctcatctatggtaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctactctggtgtttactacgattggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 665] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARYSGVYYDWGQGTLVTVSS [SEQ ID NO: 666]

TABLE 114 ET200-041 DNA Sequenceaattttatgctgactcagccccactctgtgtcggggtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccgacaactttgtgcagtggtaccagcagcgcccgggcggtgtccccaccactgtgatctttaatgatgacgaaagaccctctggcgtccctgatcggttctctggctccatcgacacctcctccaattctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgataataataatcgaggggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatgaaccctaacagtggtaacacaggctatgcacagaagttccagggcagagtcaccatgaccaggaacacctccataagcacagcctacatggagctgagcaacctgagatctgaggacacggccgtgtattactgtgcgcgctactactcttacggttacgattggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 667] Amino Acid SequenceNFMLTQPHSVSGSPGKTVTISCTGSSGSIADNFVQWYQQRPGGVPTTVIFNDDERPSGVPDRFSGSIDTSSNSASLTISGLKTEDEADYYCQSYDNNNRGVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRNTSISTAYMELSNLRSEDTAVYYCARYYSYGYDWGQGTLVTVSS [SEQ ID NO: 668]

TABLE 115 ET200-042 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagacggtcaccatctcctgcactgggggcagctccaacatcgggacaggttattttgtaaattggtaccagcaggttccaggaaaagcccccaaactcctcatcctgggtaacaataatcggccctcgggggtccctgaccgactctccggctccacgtccggcacctcagcctccctggccatcactgggctccaggctgaggatgagggtacttattactgccagtcctatgacagcagcctgagtggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtacagctgcagcagtcaggtccaggactggtgaagccctcgcagaccctctcactcacctgtggcatctccggggacagtgtctctaccaacagtgttgcttggcactggatcaggcagtccccatcgagaggccttgagtggctgggaaggacatactacaggtccaagtggtctaatgactatggagtatctgtgaaaagtcgaatcaccatcatcccagacacatccaagaaccagttctccctgcagctgaactctgtgactcccgaggacacggctgtgtattactgtgcgcgctcttcttcttggtaccagatcttcgattactggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 669] Amino Acid SequenceQSVVTQPPSVSGAPGQTVTISCTGGSSNIGTGYFVNWYQQVPGKAPKLLILGNNNRPSGVPDRLSGSTSGTSASLAITGLQAEDEGTYYCQSYDSSLSGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQSGPGLVKPSQTLSLTCGISGDSVSTNSVAWHWIRQSPSRGLEWLGRTYYRSKWSNDYGVSVKSRITIIPDTSKNQFSLQLNSVTPEDTAVYYCARSSSWYQIFDYWGQGTLVTVSS [SEQ ID NO: 670]

TABLE 116 ET200-043 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagcgacagcatagccaacaactatgttcagtggtaccagcagcgcccgggcagtgcccccaccaatgtgatctacgaagatgtccaaagaccctctggggtccctgatcggttctctgggtccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgtctactattgtcagtcttatcatagcgacaatcgttgggtgttcggcggcgggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtggagtctgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtggtggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagccgaggacacggccgtatattactgtgcgcgctctggtgcttactgggactactctgtttacgatgaatggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 671] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSDSIANNYVQWYQQRPGSAPTNVIYEDVQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEAVYYCQSYHSDNRWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSGAYWDYSVYDEWGQGTLVTVSS [SEQ ID NO: 672]

TABLE 117 ET200-044 DNA Sequencecagtctgtgttgactcagccaccctcagtgtccgtgtccccaggacagacagccaccatcgcctgttctggacataaattgggggataaatatgcttcctggtatcagcagaagtcgggccagtcccctgtgttgatcatctatcaggataataagcggccctcagggattcctgagcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctctggatgaggctgactattattgtcaggcgtgggacagtagtacttatgtggcattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctgcaggagtccggcccaggactggtgaagccttcggagaccctgtccctcacctgcgttgtctctggtggctccatcagcagtagtaactggtggagctgggtccgccagcccccagggaaggggctggagtggattggggaaatctatcatagtgggagccccaactacaacccatccctcaagagtcgagtcaccatatcagtagacaagtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcatgactactcatactttcggttacgatgcttggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 673] Amino Acid SequenceQSVLTQPPSVSVSPGQTATIACSGHKLGDKYASWYQQKSGQSPVLIIYQDNKRPSGIPERFSGSNSGNTATLTISGTQALDEADYYCQAWDSSTYVAFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQESGPGLVKPSETLSLTCVVSGGSISSSNWWSWVRQPPGKGLEWIGEIYHSGSPNYNPSLKSRVTISVDKSKNQFSLKLSSVTAADTAVYYCARMTTHTFGYDAWGQGTLVTVSS [SEQ ID NO: 674]

TABLE 118 ET200-045 DNA Sequencecagcctgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccacgattacttgtgggggaaacaacattggaagtgaaagtgtgcactggtaccaccagaagccaggccaggcccctgtgttggtcatctatgatgatgccggccggccctcagggatccctgagcgattcactggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggacagaaatagtgctcagtttgtcttcggacctgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcggtgttcatctggattggtggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 675] Amino Acid SequenceQPVLTQPPSVSVAPGKTATITCGGNNIGSESVHWYHQKPGQAPVLVIYDDAGRPSGIPERFTGSNSGNTATLTISRVEAGDEADYYCQVWDRNSAQFVFGPGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGVHLDWWGQGTLVTVSS [SEQ ID NO: 676]

TABLE 119 ET200-069 DNA Sequencecagtctgtcgtgacgcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtggttatgtcttcggaactgggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcctgtacgaaggtggttaccatggttggggttcttggctgtcttctgattcttggggtcaaggtactctggtgaccgtctcctca [SEQ ID NO: 677] Amino Acid SequenceQSVVTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGYVFGTGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLYEGGYHGWGSWLSSDSWGQGTLVTVSS [SEQ ID NO: 678]

TABLE 120 ET200-078 DNA Sequencecagtctgtgttgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgcgcgaaggggcatttgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 679] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGAFDAFDIWGQGTMVTVSS [SEQ ID NO: 680]

TABLE 121 ET200-079 DNA Sequencetcctatgagctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcttcatctataggaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtggttatctcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaatggcgactccaactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca[SEQ ID NO: 681] Amino Acid SequenceSYELTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLFIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGYLFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCANGDSNYYYGMDVWGQGTTVTVSS [SEQ ID NO: 682]

TABLE 122 ET200-081 DNA Sequencecagtctgccctgactcagcctgcctccgtgtccgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacattggtggttataactatgtctcctggtaccaacaacacccaggcaaagcccccaaactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcatctcatatacacgcacctggaacccctatgtcttcgggagtgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctgggggaggcgtggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccgtcaagctccagggaagggtctggagtgggtctctcttattagtggggatggtggtagcacatactatgcagactctgtgaagggccgattcaccatctccagagacaacagcaaaaactccctgtatctgcaaatgaacagtctgagaactgaggacaccgccttgtattactgtgcaaaagatcgggcagcagctggctactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 683] Amino Acid SequenceQSALTQPASVSGSPGQSITISCTGTSSDIGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCISYTRTWNPYVFGSGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGGGVVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSLISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRTEDTALYYCAKDRAAAGYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 684]

TABLE 123 ET200-097 DNA Sequencectgcctgtgctgactcagccaccctcagtgtccgtgtccccaggacagacagccatcatcacctgctctggagataaattgggggaaaaatatgtttcctggtatcagcagaagccaggccagtcccctgtactggtcatcgatcaagataccaggaggccctcagggatccctgagcgattctctggctccaactctgggaccacagccactctgaccatcagcgggacccaggctatggatgaggctgactattactgtcaggcgtgggacaggggtgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggagacttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttaatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggagtggtaataacataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagatagtatacggtatggcatcacctggggaggttttgactactggggccagggaaccctggtcaccgtctcctca[SEQ ID NO: 685] Amino Acid SequenceLPVLTQPPSVSVSPGQTAIITCSGDKLGEKYVSWYQQKPGQSPVLVIDQDTRRPSGIPERFSGSNSGTTATLTISGTQAMDEADYYCQAWDRGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGDLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSGISWSGNNIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDSIRYGITWGGFDYWGQGTLVTVSS [SEQ ID NO: 686]

TABLE 124 ET200-098 DNA Sequencecagcctgtgctgactcagccaccctcggtgtccaagggcttgagacagaccgccacactcacctgcactgggaacagcaacaatgttggcaacctaggagtagcttggctgcagcagcaccagggccaccctcccaaactcctatcctacaggaataacaaccggccctcagggatctcagagagattatctgcatccaggtcaggaaacacagcctccctgaccattactggactccagcctgaggacgaggctgactattactgctcagcatgggacagtagcctcagtgcttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggagtcgtggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccgtcaagctccggggaagggtctggagtgggtctctcttattaattgggatggtggtagcacctactatgcagactctgtgaagggtcgattcaccatctccagagacaacagcaaaaactccctgtatctgcaaatgaacagtctgagagctgaggacaccgccttgtattactgtgcaaaagggatgggcctgagggcgtttgactactggggccagggaaccctggtcaccgtctcctca[SEQ ID NO: 687] Amino Acid SequenceQPVLTQPPSVSKGLRQTATLTCTGNSNNVGNLGVAWLQQHQGHPPKLLSYRNNNRPSGISERLSASRSGNTASLTITGLQPEDEADYYCSAWDSSLSAWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGVVVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSLINWDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTALYYCAKGMGLRAFDYWGQGTLVTVSS [SEQ ID NO: 688]

TABLE 125 ET200-099 DNA Sequencecagtctgtgttgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcctgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtccggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcttcatgggatgacagcctgaatggccgttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggggctgaggtgaggaagcctggggcctcagtgaaggtttcctgcaagacttctggatacaccttcagttggtatgctatacattgggtgcgccaggcccccggacaaaggcttgagtggatgggatggatcaacgctggcaatggaaacacaaaatattcacagaaatttcagggcagagtcagtcttaccagggacacatccgcgagcacagcctacatggagctgagcagcctgagatctgatgacacggctgtgtattactgtgcgagacccgataattatggttcgggtggggatgtttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 689] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCASWDDSLNGRYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVRKPGASVKVSCKTSGYTFSWYAIHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVSLTRDTSASTAYMELSSLRSDDTAVYYCARPDNYGSGGDVFDIWGQGTMVTVSS [SEQ ID NO: 690]

TABLE 126 ET200-100 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactttgtgcagtggtaccagcagcgcccgggcagtgcccccacccctatgatctatgaggataacaacagaccccctggggtccctgatcggttctctgcctccgtcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgataccagcaatgtggtattcggcggggggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggagggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatgaaatgaactgggtccgccaggctccagggaaggggctggagtgggtttcatacattagtagtagtggtagtaccatatactacgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggctgtttattactgtgcacgctgggactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca[SEQ ID NO: 691] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNFVQWYQQRPGSAPTPMIYEDNNRPPGVPDRFSASVDSSSNSASLTISGLKTEDEADYYCQSYDTSNVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARWDYGMDVWGQGTTVTVSS [SEQ ID NO: 692]

TABLE 127 ET200-101 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctggggcccccgggcagagggtcaccgtctcttgttctggaagcaactccaacatcggaagtaactacgttaactggtaccagcagttcccaggaacggcccccaaactcctcatgtatagtagtagtcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccactctgaggatgaggctgattattactgtgctacatgggatgacagcctgaatgcttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaggaagcctggggcctcagtgaaggtttcctgcaagacttctggatacaccttcacttggtatgctatacattgggtgcgccaggcccccggacaaaggcttgagtggatgggatggatcaacgctggcagtggaaacacaaaatattcacagaaatttcagggcagagtcacccttaccagggacacatccgcgagcacagcgtacatggagctgagcagcctgagatctgatgacacggctgtgtattactgtgcgagacccaataactatggttcgggtggggatgtttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 693] Amino Acid SequenceQAVLTQPPSASGAPGQRVTVSCSGSNSNIGSNYVNWYQQFPGTAPKLLMYSSSQRPSGVPDRFSGSKSGTSASLAISGLHSEDEADYYCATWDDSLNAWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVRKPGASVKVSCKTSGYTFTWYAIHWVRQAPGQRLEWMGWINAGSGNTKYSQKFQGRVTLTRDTSASTAYMELSSLRSDDTAVYYCARPNNYGSGGDVFDIWGQGTMVTVSS [SEQ ID NO: 694]

TABLE 128 ET200-102 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgagtgcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaagtttcctgcaaggcttctggatacaccttcacgaactatgctctgcattgggtgcgccaggcccccggacaagggcttgagtggatggcatggatcaacggtggcaatggtaacacaaaatattcacagaacttccagggcagagtcaccattaccagggacacatccgcgagcacagcctatatggagctgagcagcctgagatctgaagacacggctgtgtattactgtgcgaaaccggaggaaacagctggaacaatccactttgactactggggccagggaaccccggtcaccgtctcctca [SEQ ID NO: 695] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTNYALHWVRQAPGQGLEWMAWINGGNGNTKYSQNFQGRVTITRDTSASTAYMELSSLRSEDTAVYYCAKPEETAGTIHFDYWGQGTPVTVSS [SEQ ID NO: 696]

TABLE 129 ET200-103 DNA Sequencecaggctgtgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcaccatcacggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgggggagggttactatgatagtagtggttattccaacggtgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 697] Amino Acid SequenceQAVLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTITVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAGEGYYDSSGYSNGDAFDIWGQGTMVTVSS [SEQ ID NO: 698]

TABLE 130 ET200-104 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaatgtggtattcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggagggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatgaaatgaactgggtccgccaggctccagggaaggggctggagtgggtttcatacattagtagtagtggtagtaccatatactacgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggctgtttattactgtgcacgctgggactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca[SEQ ID NO: 699] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNVVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARWDYGMDVWGQGTTVTVSS [SEQ ID NO: 700]

TABLE 131 ET200-105 DNA Sequencetcctatgtgctgactcagccaccctcagtgtccgtgtccccaggacagacagccagcatcacctgctctggagatagattgacgaataaatatgtttcctggtatcaacagaagccaggccagtcccctgtgttggtcatctatgaggatgccaagcggccctcagggatccctgcgcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctatggatgagtctgaatattactgtcaggcgtgggacagcagtgtggtggtttttggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggatttacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagtataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagatgaggacacggccttgtattactgtgcaaaagaccgaggggggggagttatcgttaaggatgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 701] Amino Acid SequenceSYVLTQPPSVSVSPGQTASITCSGDRLTNKYVSWYQQKPGQSPVLVIYEDAKRPSGIPARFSGSNSGNTATLTISGTQAMDESEYYCQAWDSSVVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTALYYCAKDRGGGVIVKDAFDIWGQGTMVTVSS [SEQ ID NO: 702]

TABLE 132 ET200-106 DNA Sequencetcctatgagctgactcagccacccgcagcgtctgggacccccggacagagagtcaccatctcttgttctgggggcgtctccaacatcgggagtggtgctctaaattggtaccagcaactcccaggaacggcccccaaactcctcatctatagttacaatcagcggccctcaggggtctctgaccgattctctggctccaggtctgccacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcaacctgggatgatagtgtgaatggttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctggagctgaggtgaagaagcctggggattcagtgaaggtctcctgcaagccttctggttacaattttctcaactatggtatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggattagcacttacaccggtaacacaaactatgcacagaagctgcagggcagagtcaccttcaccacagacacatccacgagcacagcctacatggagatgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgccagcagggtggtggttggtacgatgtttggggtcaaggtactctggtcaccgtctcctca[SEQ ID NO: 703] Amino Acid SequenceSYELTQPPAASGTPGQRVTISCSGGVSNIGSGALNWYQQLPGTAPKLLIYSYNQRPSGVSDRFSGSRSATSASLAISGLQSEDEADYYCATWDDSVNGWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGAEVKKPGDSVKVSCKPSGYNFLNYGINWVRQAPGQGLEWMGWISTYTGNTNYAQKLQGRVTFTTDTSTSTAYMEMRSLRSDDTAVYYCARQQGGGWYDVWGQGTLVTVSS [SEQ ID NO: 704]

TABLE 133 ET200-107 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggagagaaggtcaccatctcctgctctggaagcaacttcaatgttggaaataatgatgtatcctggtatcagcaactcccaggtgcagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctggacatcaccgggctccacagtgacgacgaggccgattattactgcggaacatgggatagcagcctgaatactgggggggtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatactatcagctgggtacgacaggcccctggacaagggcttgagtggatgggatggatcagcacttacaatggtctcacaaactatgcacagaacctccagggcagagtcaccatgactacagacacattcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattactgtgtgagagaggggtcccccgactacggtgacttcgcgtcctttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 705] Amino Acid SequenceQSVVTQPPSVSAAPGEKVTISCSGSNFNVGNNDVSWYQQLPGAAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLDITGLHSDDEADYYCGTWDSSLNTGGVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTISWVRQAPGQGLEWMGWISTYNGLTNYAQNLQGRVTMTTDTFTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFASFDYWGQGTLVTVSS [SEQ ID NO: 706]

TABLE 134 ET200-108 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctgcgcccccgggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagttcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggatttctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcgccggactccagactggggacgaggccgattattactgcggaacatgggataccagcctgagtggtttttatgtcttcggaagtgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatactatcagctgggtacgacaggcccctggacaagggcttgagtggatgggatggatcagcacttacaatggtctcacaaactatgcacagaacctccagggcagagtcaccatgactacagacacattcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattactgtgtgagagaggggtcccccgactacggtgacttcgcgtcctttgactactggggccagggaaccctggtcaccgtctcctca [SEQ ID NO: 707] Amino Acid SequenceQSVLTQPPSVSAPPGQKVTISCSGSSSNIGNNYVSWYQQFPGTAPKLLIYDNNKRPSGISDRFSGSKSGTSATLGIAGLQTGDEADYYCGTWDTSLSGFYVFGSGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTISWVRQAPGQGLEWMGWISTYNGLTNYAQNLQGRVTMTTDTFTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFASFDYWGQGTLVTVSS [SEQ ID NO: 708]

TABLE 135 ET200-109 DNA Sequencectgcctgtgctgactcagccaccctcagcgtctgcgacccccgggcagagggtcaccatctcttgttctggaaccacctccaacatcggaagtaatactgtacactggtaccagcagctcccagggacggcccccaaactcctcatctataataataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctacatattcctgtgcaacatgggatgacagcctgagtggtgtggtcttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagagatcccgcctacggtgactacgagtatgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca [SEQ ID NO: 709] Amino Acid SequenceLPVLTQPPSASATPGQRVTISCSGTTSNIGSNTVHWYQQLPGTAPKLLIYNNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEATYSCATWDDSLSGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDPAYGDYEYDAFDIWGQGTMVTVSS [SEQ ID NO: 710]

TABLE 136 ET200-110 DNA Sequencecagtctgtgttgacgcagccgccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaactaatggtgtaaactggttccagcagttcccaggaacggcccccaaactcctcatctatactaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgcggatgaggctgattattactgtgcagtgtgggaccacagcctgaatggtccggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagaggggccggttttgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 711] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGTNGVNWFQQFPGTAPKLLIYTNDQRPSGVPDRFSGSKSGTSASLAISGLQSADEADYYCAVWDHSLNGPVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGAGFDAFDIWGQGTMVTVSS [SEQ ID NO: 712]

TABLE 137 ET200-111 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgagactgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagaggggctagatgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 713] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDETDYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGLDAFDIWGQGTMVTVSS [SEQ ID NO: 714]

TABLE 138 ET200-112 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatgtatagtaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattattgtgcagcatgggatgacagcctgaatggttatgtcttcgcagctgggacccagctcaccgttttaagttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagaggggctagatgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 715] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLMYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFAAGTQLTVLSSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGLDAFDIWGQGTMVTVSS [SEQ ID NO: 716]

TABLE 139 ET200-113 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcactggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgagtgctgcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacagctttaccagctatactatcagctgggttcgacaggcccctggacaaggccttgagtggatgggatgggtcagcacttacaatggtctcagaaactatgcacagaacctccagggcagagtcaccatgactacagacacactcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattattgtgtgagagaggggtcccccgactacggtgacttcgcggcctttgactactggggccagggcaccctggtcaccgtctcctca [SEQ ID NO: 717] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYSFTSYTISWVRQAPGQGLEWMGWVSTYNGLRNYAQNLQGRVTMTTDTLTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFAAFDYWGQGTLVTVSS [SEQ ID NO: 718]

TABLE 140 ET200-114 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgagacccccgggcagagggtcaccatctcttgttctggaagcaggtccaacatcggaactaatattgtacactggtaccagcagcgcccaggaatggcccccaaactcctcacttatggtagtcggcggccctcaggggtcccggaccgattctctggctccaagtttggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattattgtgcagcatgggatgacagtctgaatggtccggctttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagacggtgggggctactttgactactggggccagggaaccctggtcaccgtctcctca[SEQ ID NO: 719] Amino Acid SequenceQAVLTQPPSASETPGQRVTISCSGSRSNIGTNIVHWYQQRPGMAPKLLTYGSRRPSGVPDRFSGSKFGTSASLAISGLQSEDEADYYCAAWDDSLNGPAFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGGGYFDYWGQGTLVTVSS [SEQ ID NO: 720]

TABLE 141 ET200-115 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaatatcggggcacgttatgatgtacactggtaccagcaactcccaggaacagccccccgactcctcatctctgctaactacgatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagtgtgagtgcttgggtgttcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctggggctgaagtgaaggagcctggggcctcagtgaggatctcctgccaggcatctggatacaacttcatcagttattatatgcactgggtgcggcaggcccctgggcaaggtcttgagtggatgggcaccatcaacccaggcagtggtgagacagactactcacagaagttgcagggcagagtcaccatgaccagggacccgtccacgggtacattcgacatggggctgagcagcctgacatctggggacacggccgtctattattgtgcgacaggtctcatcagaggagctagcgatgcttttaatatctggggccgggggacaatggtcaccgtctcttca [SEQ ID NO: 721] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSSSNIGARYDVHWYQQLPGTAPRLLISANYDRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSVSAWVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKEPGASVRISCQASGYNFISYYMHWVRQAPGQGLEWMGTINPGSGETDYSQKLQGRVTMTRDPSTGTFDMGLSSLTSGDTAVYYCATGLIRGASDAFNIWGRGTMVTVSS [SEQ ID NO: 722]

TABLE 142 ET200-116 DNA Sequencecagcctgtgctgactcagccaccctcagtgtccgtgtccccaggacagacggccgccatcccctgttctggagataagttgggggataaatttgcttcctggtatcagcagaagccaggccagtcccctgtgctggtcatctatcaagatactaagcggccctcagggatccctgagcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctatggatgaggctgactattactgtcagacgtgggccagcggcattgtggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtacagctgcagcagtcaggtccaggactggtgaagccctcgcagaccctctcactcacctgtgccatctccggggacagtgtctctagcaacagtgctgcttggaactggatcaggcagtccccatcgagaggccttgagtggctgggaaggacatactacaggtccaagtggtataatgattatgcagtatctgtgaaaagtcgaataaccatcaacccagacacatccaagaaccagttctccctgcagctgaactctgtgactcccgaggacacggctgtgtattactgtgcaagagagcgcagtggctggaagggatttgactactggggccagggaaccctggtcaccgtctcctca[SEQ ID NO: 723] Amino Acid SequenceQPVLTQPPSVSVSPGQTAAIPCSGDKLGDKFASWYQQKPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQTWASGIVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCARERSGWKGFDYWGQGTLVTVSS [SEQ ID NO: 724]

TABLE 143 ET200-117 DNA Sequencegatgttgtgatgactcagtctccaccctccctgtccgtcacccctggagagccggcctccatcacctgcaggtctagtcagagcctcctggaaagaaatgcatacaactacttggattggtacctgcagaggccaggacagtctccacagctcctgatctacttgggttctaatcgggccgccggggtccctgacaggttcagtggcagtggatcaggcagagattttacactgaaaatcagcagagtggagcctgaggatgttggggtttattactgcatgcaagctctacaagctccgttcactttcggcggagggaccaaggtggagatcaaacgttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtggtggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagccgaggacacggccgtatattactgtgcgaaatggggcccgtttcaggatgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 725] Amino Acid SequenceDVVMTQSPPSLSVTPGEPASITCRSSQSLLERNAYNYLDWYLQRPGQSPQLLIYLGSNRAAGVPDRFSGSGSGRDFTLKISRVEPEDVGVYYCMQALQAPFTFGGGTKVEIKRSRGGGGSGGGGSGGGGSLEMAEVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKWGPFQDAFDIWGQGTMVTVSS [SEQ ID NO: 726]

TABLE 144 ET200-118 DNA Sequencecaggctgtgctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactatgtctcctggtaccaacagcacccgggcaaagcccccaaactcatgatttatgaggtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcaccccttatgtcttcggagcagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagccaggtggacagcagtggcatcagaccaccactttgactactggggccagggaacgctggtcaccgtctcctca [SEQ ID NO: 727] Amino Acid SequenceQAVLTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTPYVFGAGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKARWTAVASDHHFDYWGQGTLVTVSS [SEQ ID NO: 728]

TABLE 145 ET200-119 DNA Sequencecaggctgtgcttactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagagattgggactacatggacgtctggggcaaagggaccacggtcaccgtctcctca[SEQ ID NO: 729] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDWDYMDVWGKGTTVTVSS [SEQ ID NO: 730]

TABLE 146 ET200-120 DNA Sequencetcctatgagctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgagagacctatctcggggagctaacccgcattactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 731] Amino Acid SequenceSYELTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDLSRGANPHYYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 732]

TABLE 147 ET200-121 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccgtctcctgcactgggagcagatccaacatcggggcaggatatgatgtacactggtaccagcaacttccaggaacagcccccaaactcctcatctatggaaatagtaatcggcctccaggggtccctgaccgattctctgggtctaagtctggcacctcagcctccctggtcatcactgggctccaggctgaggatgccgctgattattactgccagtcctatgacaacactgtgcgtgaatcaccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtacagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcaacagagagtaatttagtgtcccggcactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 733] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTVSCTGSRSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPPGVPDRFSGSKSGTSASLVITGLQAEDAADYYCQSYDNTVRESPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATESNLVSRHYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 734]

TABLE 148 ET200-122 DNA Sequencectgcctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaaccagctccaacatcggaagtaattctgtagactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgaatctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggatacaccttcaccggctactatatgcactgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcaaccctaacagtggtggcacaaactatgcacagaagtttcagggcagggtcaccatgaccagggacacgtccatcagcacagcctacatggagctgagcaggctgagatctgacgacacggccgtgtattactgtgcgagagattacggatactatggttcggggagttattcgagcggccccctttactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 735] Amino Acid SequenceLPVLTQPPSASGTPGQRVTISCSGTSSNIGSNSVDWYQQLPGTAPKLLIYSNNQRPSGVPDRISGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYGYYGSGSYSSGPLYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 736]

TABLE 149 ET200-123 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatgtataataatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctcaatggttatgtcttcggacctgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtggagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgagagacctatctcggggagctaacccgcattactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctca [SEQ ID NO: 737] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLMYNNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGPGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDLSRGANPHYYYYYGMDVWGQGTTVTVSS [SEQ ID NO: 738]

TABLE 150 ET200-125 DNA Sequenceaattttatgctgactcagccccacgctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagtattgccagcaactatgtgcagtggtaccagcagcgcccgggcagttccccccgcactgtgatttatgaggataatcaaagaccctctggggtccctggtcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgattccaccagtgtgcttttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagccagggtcctcggtgaaggtctcctgcaaggcctcgggaggcaccttcagcagcaattctctcagctgggtgcgacaggcccctggacaagggcttgagtggatgggaaggatcttccctatcctgggtataacaaactatgcacagaagttccagggcagagtcacgattaccgcggacaaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtctattactgtgcgagaggaaactaccaatggtatgatgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 739] Amino Acid SequenceNFMLTQPHAVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPRTVIYEDNQRPSGVPGRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTSVLFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSNSLSWVRQAPGQGLEWMGRIFPILGITNYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARGNYQWYDAFDIWGQGTMVTVSS [SEQ ID NO: 740]

TABLE 151 ET200-005 DNA Sequencecagcctgtgctgactcagccaccctcagtgtcagtggtcccaggaaagacggccaggattacctgtgggggaaaaaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtggtggtcatccattatgatagtgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccaactatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacataagctccagggcagagtcaccatgaccacagacacatccacgagcacagccaacatggagctgaggagcctgagacctgacgacactgccgtgtattactgtgcgcgctcttacttcggttctcatgattactggggtcaaggtactctggtgaccgtctcctca[SEQ ID NO: 741] Amino Acid SequenceQPVLTQPPSVSVVPGKTARITCGGKNIGSKSVHWYQQKPGQAPVVVIHYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGISWVRQAPGQGLEWMGWISAYNGNTNYAHKLQGRVTMTTDTSTSTANMELRSLRPDDTAVYYCARSYFGSHDYWGQGTLVTVSS [SEQ ID NO: 742]

TABLE 152 ET200-124 DNA Sequencetcctatgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggatttcctgtgggggaaacgacattggaagtaaaagtgttttctggtatcagcagaggccaggccaggcccctgtgttggtcgtctatgatgatagcgaccggccctcagggctccctgagcgattctctggcttcaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaagtgtgggatagtagtagtgatcattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagatataacctatggttcggggagttatggtgcttttgatatctggggccaagggacaatggtcaccgtctcttca[SEQ ID NO: 743] Amino Acid SequenceSYVLTQPPSVSVAPGKTARISCGGNDIGSKSVFWYQQRPGQAPVLVVYDDSDRPSGLPERFSGFNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDITYGSGSYGAFDIWGQGTMVTVSS [SEQ ID NO: 744]

XII. Exemplary Extracellular Antigen-Binding Domains (e.g., scFvs)Comprising a Heavy Chain Variable Region, a Light Chain Variable Region,a Linker Peptide and a His-tag and HA-tag

TABLE 153 ET200-001 DNA Sequencecagtctgtgttgacgcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtgtatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcgaaggtccgtacgacggtttcgattcttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 745] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGPYDGFDSWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:746]

TABLE 154 ET200-002 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattctgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggcactgaggtgaagaagcctggggcctcagtgagggtcgcctgcaaggcttctggttacccctttaacaaatatgacatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggaggcatcatccctatctttcgtacaacaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtatattactgtgcgcgcgaatggttctactgggatatctggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 747] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNSVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGTEVKKPGASVRVACKASGYPFNKYDINWVRQAPGQGLEWMGGIIPIFRTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREWFYWDIWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPD YAS [SEQ ID NO:748]

TABLE 155 ET200-003 DNA Sequencecagtctgtgttgactcagccaccctcagtgtccgtgtccccaggacagacagccagcatctcctgctctggaaataaattggggactaagtatgtttactggtatcagaagaggccaggccagtcccctgtgttggtcatgtatgaagataatcagcggccctcagggatcccggagcggttctctggctccaactctgggaacacagccactctgaccatcagagggacccagactgtggatgaggctgactattactgtcaggcgtgggactccgacactttcgtggtcttcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagaccgggggaggcgtggtccagcctgggaggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatggcatgcactgggtccgccaggctccaggcaaggggctggagtgggtggcagttatatcacatgatggaagtaataaatactacgcagactccgtgaagggccgattcaccatctccagagacaattccaaggacacgctgtatctgcaaatgaacagcctgagaggtgaggacacggccgtatattactgtgcgcgctctaaccagtggtctggttacttctctttcgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 749] Amino Acid SequenceQSVLTQPPSVSVSPGQTASISCSGNKLGTKYVYWYQKRPGQSPVLVMYEDNQRPSGIPERFSGSNSGNTATLTIRGTQTVDEADYYCQAWDSDTFVVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISHDGSNKYYADSVKGRFTISRDNSKDTLYLQMNSLRGEDTAVYYCARSNQWSGYFSFDYWGQGTLVTVSSTSGQAGQHHHHHHGAY PYDVPDYAS [SEQ IDNO: 750]

TABLE 156 ET200-006 DNA Sequencetcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtggtggtcatccattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccacctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcaacacttacaatggtcacacaaactatgcacagaagctccagggcagagccacaatgaccgcagacacatccacgaacacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgcgttatctacggttctggtgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 751] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVVVIHYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGISWVRQAPGQGLEWMGWINTYNGHTNYAQKLQGRATMTADTSTNTAYMELRSLRSDDTAVYYCARVIYGSGDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:752]

TABLE 157 ET200-007 DNA Sequencetcctatgtgctgactcagccactctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaactgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatcgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctgcaggagtcgggcccaggactggtgaagccttcggagaccctgtccctcacctgcaatgtctctggttactccatcagcagtggttacttttggggctggatccggcagcccccagggaaggggctggagtggattgggagtatctatcatagtaggagcacctactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgaactctgtgaccgccgcagacacggccgtgtattactgtgcgcgcggttacggttacttcgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:753] Amino Acid SequenceSYVLTQPLSVSVAPGKTARITCGGNNIGSKTVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHRVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQESGPGLVKPSETLSLTCNVSGYSISSGYFWGWIRQPPGKGLEWIGSIYHSRSTYYNPSLKSRVTISVDTSKNQFSLKLNSVTAADTAVYYCARGYGYFDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 754]

TABLE 158 ET200-008 DNA Sequencecaatctgccctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactatgtctcctggtaccaacaacacccaggcaaagcccccaaactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcacttcgaaggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggtgtggtacggcctggggggtccctgagactctcctgtgcagcctctggattcacctttggtgattatggcatgagctgggtccgccaagctccagggaaggggctggagtgggtctctggtattaattggaatggtggtagcacaggttatgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagccgaggacacggccgtatattactgtgcgcgctctaaatacaacttccatgtttactacgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 755] Amino Acid SequenceQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTSKVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGVVRPGGSLRLSCAASGFTFGDYGMSWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSKYNFHVYYDYWGQGTLVTVSSTSGQAGQHHHHHHGA YPYDVPDYAS [SEQ IDNO: 756]

TABLE 159 ET200-009 DNA Sequencecagtctgtgttgacgcagccaccctcagcgtctgggacccccgggcagacagtcaccatctcttgttctggaagcaactccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcctcatctataggaataatcagcggccctcaggggtccctgaccgattctcaggctccaagtctggcacctcagcctccctggccatcagtgggctccgctccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtgcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgctcttctggtaacatggtttcttggaaagatatgtggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 757] Amino Acid SequenceQSVLTQPPSASGTPGQTVTISCSGSNSNIGSNYVYWYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARSSGNMVSWKDMWGQGTLVTVSSTSGQAGQHHHHHHG AYPYDVPDYAS [SEQ IDNO: 758]

TABLE 160 ET200-010 DNA Sequencecaatctgccctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactctgtctcctggtaccaacaacacccaggcaaagcccccagactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcacccctttagtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcggtgctgttgcttaccatgattggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:759] Amino Acid SequenceQSALTQPASVSGSPGQSITISCTGTSSDVGGYNSVSWYQQHPGKAPRLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTPLVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGAVAYHDWGQGTLVTVSSTSGQAGQHHHHHHGAYPYD VPDYAS [SEQ ID NO:760]

TABLE 161 ET200-011 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagagggtcaccatctcctgctctggaagcagctccaacatttcgatttatgatgtatcctggtatcagcagctcccaggaacagcccccaaactcctcatttatggcaataataagcgaccctcggggattgctgaccgattctctggctccacgtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatgacagtctgagtgggggggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcaatctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcgaggcttctggaggcaccctcagcagctatgctatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatgtttggtacagcacactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgaaaacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtgttcattacgcttctttcgatcattggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 761] Amino Acid SequenceQSVVTQPPSVSAAPGQRVTISCSGSSSNISIYDVSWYQQLPGTAPKLLIYGNNKRPSGIADRFSGSTSGTSATLGITGLQTGDEADYYCGTWDDSLSGGVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGSSVKVSCEASGGTLSSYAINWVRQAPGQGLEWMGGIIPMFGTAHYAQKFQGRVTITADESTKTAYMELSSLRSEDTAVYYCARGVHYASFDHWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDV PDYAS [SEQ ID NO:762]

TABLE 162 ET200-012 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctgcggccgcaggacagaaggtcaccatctcctgctctggaagcgactccaacattgggaataattatgtgtcctggtatcaacacctcccagggacagcccccaaactcctcatttatgacgttaaaaatcgaccctcagggattcctgaccggttctccggctccaagtctggctcgtcagccaccctaggcatcgccggactccagcctggggacgaggccgattattactgcggaacatgggacagtcggctggatgcctatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcaatctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaagacttctggtttcccctttaatatctttggaatcacctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcggttacaacggtaacacagactacccacagaagttccagggcagagtcaccatgtccacagacacatccacgagtacagcctacatggagctgaggaacctgaaatctgacgacacggccgtgtattactgtgcgcgcggtgcttacggtggtatggatacttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 763] Amino Acid SequenceQSVLTQPPSVSAAAGQKVTISCSGSDSNIGNNYVSWYQHLPGTAPKLLIYDVKNRPSGIPDRFSGSKSGSSATLGIAGLQPGDEADYYCGTWDSRLDAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGASVKVSCKTSGFPFNIFGITWVRQAPGQGLEWMGWISGYNGNTDYPQKFQGRVTMSTDTSTSTAYMELRNLKSDDTAVYYCARGAYGGMDTWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:764]

TABLE 163 ET200-013 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcacctccaacatcggggcaggttatgatgtacactggtatcagcagcttccaggaacagcccccaaactcctcatctatactaacaactttcggccctcaggggtccctgaccgattctctgcctccaagtctggcacttcagcttccctggccatcactggtctccaggctgaggatgaggctgattattactgcggaacatgggatagcagcctgagtgccgttgtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctggaactgaggtgaagaagcctggggcctcagtgaaagtctcctgcaaggcttctggttacatgtttaccagttatggtctcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgctaacaatggtaagacaaattatgctaagaaattccaggacagagtcaccatgaccagagacacttccacgagcacaggctacatggaactgaggagcctgagatctgacgacacggccgtatattactgtgcgcgccatatcggtggttcttacttcgatcgttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 765] Amino Acid SequenceQSVVTQPPSVSGAPGQRVTISCTGSTSNIGAGYDVHWYQQLPGTAPKLLIYTNNFRPSGVPDRFSASKSGTSASLAITGLQAEDEADYYCGTWDSSLSAVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGTEVKKPGASVKVSCKASGYMFTSYGLNWVRQAPGQGLEWMGWISANNGKTNYAKKFQDRVTMTRDTSTSTGYMELRSLRSDDTAVYYCARHIGGSYFDRWGQGTLVTVSSTSGQAGQHHHHHHGA YPYDVPDYAS [SEQ IDNO: 766]

TABLE 164 ET200-014 DNA Sequencetcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagactgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtgatggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagacgaggacacggccgtatattactgtgcgcgctctcatgaagctaacctggttggtgattggtggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 767] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSDGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARSHEANLVGDWWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:768]

TABLE 165 ET200-015 DNA Sequencecagtctgtggtgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctacggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgctggggtggtttcggtgctgttgatcattggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 769] Amino Acid SequenceQSVVTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARWGGFGAVDHWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:770]

TABLE 166 ET200-016 DNA Sequencetcttctgagctgactcaggaccctgctgtgtctgtggccttgggacagacagtcaagatcacgtgccaaggagacagcctcacagactaccatgcaacctggtaccagcagaagccaggacaggcccctgtcgctgtcatctatgctacaaacaaccggcccactgggatcccagaccgattctctggttccagttccggaaacacagcttctttgaccatcactggggctcaggcggaagatgaggctgactattactgtaattcccgggacagcggcacggacgaagtgttattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagactgggggaggcctggtcaagcctggggggtccctgagactctcctgtgcagcctctggattcaccttcagtagctatagcatgaactgggtccgccaggctccagggaaggggctggagtgggtctcatccattagtagtagtagtagttacatatactacgcagactcagtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggccgtgtattactgtgcgcgcggtcagggttacgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:771] Amino Acid SequenceSSELTQDPAVSVALGQTVKITCQGDSLTDYHATWYQQKPGQAPVAVIYATNNRPTGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSGTDEVLFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGQGYDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDY AS [SEQ ID NO: 772]

TABLE 167 ET200-017 DNA SequenceTcctatgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcgtctatgatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgagcatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatactgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgctactacccgggtatggatatgtggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:773] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTATLSISRVEAGDEADYYCQVWDSSSDHTVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARYYPGMDMWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDY AS [SEQ ID NO: 774]

TABLE 168 ET200-018 DNA SequenceCaggctgtgctgactcagccgccctcaacgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcgggagaaatggtgtaaactggtaccagcagctcccaggagcggcccccaaagtcctcatctataatgataatcagcgaccctcaggggtccctgaccgagtctctggctcccagtctggctcctcaggcaccctggccatcgatgggcttcggtctgaggatgaggctgattattactgtgcggcatgggatgacagcctgcatggtgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcaatgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtggttacggtgattcttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 775] Amino Acid SequenceQAVLTQPPSTSGTPGQRVTISCSGSSSNIGRNGVNWYQQLPGAAPKVLIYNDNQRPSGVPDRVSGSQSGSSGTLAIDGLRSEDEADYYCAAWDDSLHGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKVSGYTLNELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARGGYGDSWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:776]

TABLE 169 ET200-019 DNA SequenceAattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattcttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcaatctggggctgaggtgaagaggcctgggtcctcggtgaaggtctcctgcacggcttctggaggcaccttcagcagcgatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggaggaatcatccctatgtttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcgaaggttactactacccgtctgcttacctgggttctgttctgaacgacatctcttctgtttacgatgaatggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 777] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNSWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKRPGSSVKVSCTASGGTFSSDAISWVRQAPGQGLEWMGGIIPMFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGYYYPSAYLGSVLNDISSVYDEWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 778]

TABLE 170 ET200-020 DNA SequenceCagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcacctccaacattggaaataatgatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcgtgagtgcttcttgggtcttcggcagagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatccacagaagctccagggcagagtcaccatgaccacagacccatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgctctatgacttctttcgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 779] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSTSNIGNNDVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSVSASWVFGRGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYPQKLQGRVTMTTDPSTSTAYMELRSLRSDDTAVYYCARSMTSFDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYD VPDYAS [SEQ ID NO:780]

TABLE 171 ET200-021 DNA SequenceCagtctgtgttgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcaactccaacattgggaataattatgtatcctggtatcagcaactcccagggacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaggtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatggaataccactgtgactcctggctatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacaccgccatgtattactgtgcgcgctctgtttacgacctggatacttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 781] Amino Acid SequenceQSVLTQPPSVSAAPGQKVTISCSGSNSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSRSGTSATLGITGLQTGDEADYYCGTWNTTVTPGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAMYYCARSVYDLDTWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:782]

TABLE 172 ET200-022 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgggggccccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtcttggggaggctcggaacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagcggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaattccctgtatctgcaaatgaacagtctgagagctgaggacaccgccatgtattactgtgcgcgctaccgtcaggttggttctgcttacgattcttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 783] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLGAPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSWGGSEQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAMYYCARYRQVGSAYDSWGQGTLVTVSSTSGQAGQHHHHHHGAY PYDVPDYAS [SEQ IDNO: 784]

TABLE 173 ET200-023 DNA Sequencectgcctgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtatcagcagaagccaggccaggcccctgtgctggtcgtctatgctgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagttatcataattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgagcagcctgagatctgaggacaccgccatgtattactgtgcgcgctactggggtttcggtgtttctgatcgttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 785] Amino Acid SequenceLPVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYADSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSYHNYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELSSLRSEDTAMYYCARYWGFGVSDRWGQGTLVTVSSTSGQAGQHHHHHHGAYP YDVPDYAS [SEQ IDNO: 786]

TABLE 174 ET200-024 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccccgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgacagcagcaatctttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctacaactactactactacgattcttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 787] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNLWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARYNYYYYDSWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:788]

TABLE 175 ET200-025 DNA Sequencegacatccagatgacccagtctccatcctccctgtctgcatctgtaggagacagagtcaccatcacttgccgggcaagtcagagcattagcagctatttaaattggtatcagcagaaaccagggaaagcccctaagctcctgatctatgctgcatccagtttgcaaagtggggtcccatcaaggttcagtggcagtggatctgggacagatttcactctcaccatcagcagtctgcaacctgaagattttgcaacttactactgtcaacagagttacagtaccccattcactttcggccctgggaccaaagtggatatcaaacgttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacaccgccatgtattactgtgcgcgctactggggttacgactcttacgatgaatggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:789] Amino Acid SequenceDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIKRSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAMYYCARYWGYDSYDEWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDYA S [SEQ ID NO: 790]

TABLE 176 ET200-026 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcaacaaccattactacaacgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 791] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARNNHYYNDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:792]

TABLE 177 ET200-027 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagggggtcaccatcccctgcactgggagcagctccaacatcggggcaggttatgatgtacactggtaccagcagcttccagggacagcccccaaactcctcatctatggtaacaacaatcggccctcaggggtccctgaccgcttctctggctccaggtctggctcctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtgatgtggtattcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctggggctacagtgaaaatctcctgcaaggtttctggatacaccttcaccgactactacatgcactgggtgcaacaggcccctggaaaagggcttgagtggatgggacttgttgatcctgaagatggtgaaacaatatacgcagagaagttccagggcagagtcaccataaccgcggacacgtctacagacacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgctactggtcttactctttcgactacctgtacatgccggaaggtaacgattggtggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 793] Amino Acid SequenceQSVLTQPPSVSGAPGQGVTIPCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNNNRPSGVPDRFSGSRSGSSASLAITGLQAEDEADYYCQSYDSSLSDVVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGATVKISCKVSGYTFTDYYMHWVQQAPGKGLEWMGLVDPEDGETIYAEKFQGRVTITADTSTDTAYMELSSLRSEDTAVYYCARYWSYSFDYLYMPEGNDWWGQGTLVTVSSTSGQAGQH HHHHHGAYPYDVPDYAS[SEQ ID NO: 794]

TABLE 178 ET200-028 DNA Sequencecagtctgtgttgactcagccacccgcagcgtctgggacccccggacagagagtcaccatctcttgttctgggggcgtctccaacatcgggagtggtgctctaaattggtaccagcaactcccaggaacggcccccaaactcctcatctatagttacaatcagcggccctcaggggtctctgaccgattctctggctccaggtctgccacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcaacctgggatgatagtgtgaatggttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggagctgaggtgaagaagcctggggattcagtgaaggtctcctgcaagccttctggttacaattttctcaactatggtatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggattagcacttacaccggtaacacaaactatgcacagaagctgcagggcagagtcaccttcaccacagacacatccacgagcacagcctacatggagatgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcgacctgtactactacgaaggtgttgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 795] Amino Acid SequenceQSVLTQPPAASGTPGQRVTISCSGGVSNIGSGALNWYQQLPGTAPKLLIYSYNQRPSGVSDRFSGSRSATSASLAISGLQSEDEADYYCATWDDSVNGWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGDSVKVSCKPSGYNFLNYGINWVRQAPGQGLEWMGWISTYTGNTNYAQKLQGRVTFTTDTSTSTAYMEMRSLRSDDTAVYYCARDLYYYEGVDYWGQGTLVTVSSTSGQAGQHHHHHHGA YPYDVPDYAS [SEQ IDNO: 796]

TABLE 179 ET200-029 DNA Sequencecaggctgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccagggttacctgtgggggaaacaacattggaagtgaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgttggtcatctattatgataccgaccggccctcagggatccctgagcgattctctggctcccactctgggaccacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagggatcatgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctgggggaggcgtggtccagcctgggaggtccctgagactctcctgtgcggcctctggattcaccttcagtagctatgctatgcactgggtccgccaggctccaggcaagggactggagtgggtggcagttatatcatatgatggaagcaataaatactacgcagactccgtgaagggcctattcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagctgaggacacggccgtgtattactgtgcgcgctcttacttcacttctggtttctacgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 797] Amino Acid SequenceQAVLTQPPSVSVAPGKTARVTCGGNNIGSESVHWYQQKPGQAPVLVIYYDTDRPSGIPERFSGSHSGTTATLTISRVEAGDEADYYCQVWDSSRDHVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGLFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSYFTSGFYDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ IDNO: 798]

TABLE 180 ET200-030 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagttccaacatcggggcaggttatgatgtaaattggtatcagcagtttccaggaacagcccccaaactcctcatctatggtaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggctcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcatgtcttctatgtactacgattggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 799] Amino Acid SequenceQSVVTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVNWYQQFPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGSYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGASVKVSCKASGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARMSSMYYDWGQGTLVTVSSTSGQAGQHHHHHHGAY PYDVPDYAS [SEQ IDNO: 800]

TABLE 181 ET200-031 DNA Sequencetcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagactgggggaggcttggtcaagcctggagggtccctgagactctcctgtgcagcctctggattcaccgtcagtgactactacatgagctggatccgccaggctccagggaagggcctggagtggatttcatacattagtggtagtggtaatagcatatactacgcagactctgtgaagggccgattcaccatctccagggacaacgccaagaactcactggatctgcaaatgaccagcctgagagccgaggacacggccgtatattactgtgcgcgctctactaaattcgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 801]Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVETGGGLVKPGGSLRLSCAASGFTVSDYYMSWIRQAPGKGLEWISYISGSGNSIYYADSVKGRFTISRDNAKNSLDLQMTSLRAEDTAVYYCARSTKFDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 802]

TABLE 182 ET200-032 DNA Sequencectgcctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacgtcggaagttacactgtaaactggtaccggcaactcccaggaacggcccccacactcctcatctataataataatcagcggccctcaggggtccctgaccgattctctgactccaagtctggcacctcggcctccctgaccattagtgggctccagcctgaggatgaggctgattattattgtgcagcatgggatgacaggctgggtggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggagcagaggtgaaaaagccgggggagtctctgaagatctcctgtaagggttctggatacagctttaccaactactggatcggctgggtgcgccagatgcccgggaaaggcctggagtggatggggatcatctatcctggtgactctgataccagatacagcccgtccttccaaggccaggtcaccatctcagccgacaagtccatcagcaccgcctacctacagtggagcagcctgaaggcctcggacaccgccatgtattactgtgcgcgctctactggttcttctcatatgtctgatgaatggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 803] Amino Acid SequenceLPVLTQPPSASGTPGQRVTISCSGSSSNVGSYTVNWYRQLPGTAPTLLIYNNNQRPSGVPDRFSDSKSGTSASLTISGLQPEDEADYYCAAWDDRLGGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARSTGSSHMSDEWGQGTLVTVSSTSGQAGQHHHHHHGAYPYD VPDYAS [SEQ ID NO:804]

TABLE 183 ET200-033 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaatcattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaagtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggagatcactcatagtggaaggtccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgctcttctatcatgtctgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:805] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNHWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEITHSGRSNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARSSIMSDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDY AS [SEQ ID NO: 806]

TABLE 184 ET200-034 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcacctccaacatcggggcaggttatgatgtacactggtaccagcagcttccaggaacagcccccaaactcctcatcaacaataacaggaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatggcagcctgactggtgcagtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcatgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgcggttctgctctggaccattacgatcgttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 807] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSTSNIGAGYDVHWYQQLPGTAPKLLINNNRNRPSGVPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDGSLTGAVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSALDHYDRWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:808]

TABLE 185 ET200-035 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcaccaattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctacaactactacttcaacgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 809] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTNWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARYNYYFNDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPD YAS [SEQ ID NO:810]

TABLE 186 ET200-037 DNA Sequencetcctatgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccaggattacctgtgggggaaacaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtgctggtcatctattatgatagcgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccagatgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacactgccgtgtattactgtgcgcgctctatgttcggtgctcatgattcttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 811] Amino Acid SequenceSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQMQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARSMFGAHDSWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:812]

TABLE 187 ET200-038 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaacatcggggcaggttttgatgtacactggtaccagctacttccaggaacagcccccaaactcctcatctatgctaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctcctggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggtgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcaatctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgcggtgcttctttcgaccgtcatgataactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 813] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGFDVHWYQLLPGTAPKLLIYANSNRPSGVPDRFSGSKSGTSASLAITGLLAEDEADYYCQSYDSSLSGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGASFDRHDNWGQGTLVTVSSTSGQAGQHHHHHHGAYPYD VPDYAS [SEQ ID NO:814]

TABLE 188 ET200-039 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagttcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgcgctctaactactactacaacgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 815] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARSNYYYNDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPD YAS [SEQ ID NO:816]

TABLE 189 ET200-040 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaacatcggggcaggttatgatgtacactggtaccagcagcttccaggaacagcccccaaactcctcatctatggtaacagcaatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagcctgagtggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacactgccgtgtattactgtgcgcgctactctggtgtttactacgattggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 817] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCARYSGVYYDWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:818]

TABLE 190 ET200-041 DNA Sequenceaattttatgctgactcagccccactctgtgtcggggtctccggggaagacggtaaccatctcctgcaccggcagcagtggcagcattgccgacaactttgtgcagtggtaccagcagcgcccgggcggtgtccccaccactgtgatctttaatgatgacgaaagaccctctggcgtccctgatcggttctctggctccatcgacacctcctccaattctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgataataataatcgaggggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatgaaccctaacagtggtaacacaggctatgcacagaagttccagggcagagtcaccatgaccaggaacacctccataagcacagcctacatggagctgagcaacctgagatctgaggacacggccgtgtattactgtgcgcgctactactcttacggttacgattggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 819] Amino Acid SequenceNFMLTQPHSVSGSPGKTVTISCTGSSGSIADNFVQWYQQRPGGVPTTVIFNDDERPSGVPDRFSGSIDTSSNSASLTISGLKTEDEADYYCQSYDNNNRGVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRNTSISTAYMELSNLRSEDTAVYYCARYYSYGYDWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:820]

TABLE 191 ET200-042 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctggggccccagggcagacggtcaccatctcctgcactgggggcagctccaacatcgggacaggttattttgtaaattggtaccagcaggttccaggaaaagcccccaaactcctcatcctgggtaacaataatcggccctcgggggtccctgaccgactctccggctccacgtccggcacctcagcctccctggccatcactgggctccaggctgaggatgagggtacttattactgccagtcctatgacagcagcctgagtggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtacagctgcagcagtcaggtccaggactggtgaagccctcgcagaccctctcactcacctgtggcatctccggggacagtgtctctaccaacagtgttgcttggcactggatcaggcagtccccatcgagaggccttgagtggctgggaaggacatactacaggtccaagtggtctaatgactatggagtatctgtgaaaagtcgaatcaccatcatcccagacacatccaagaaccagttctccctgcagctgaactctgtgactcccgaggacacggctgtgtattactgtgcgcgctcttcttcttggtaccagatcttcgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 821] Amino Acid SequenceQSVVTQPPSVSGAPGQTVTISCTGGSSNIGTGYFVNWYQQVPGKAPKLLILGNNNRPSGVPDRLSGSTSGTSASLAITGLQAEDEGTYYCQSYDSSLSGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQSGPGLVKPSQTLSLTCGISGDSVSTNSVAWHWIRQSPSRGLEWLGRTYYRSKWSNDYGVSVKSRITIIPDTSKNQFSLQLNSVTPEDTAVYYCARSSSWYQIFDYWGQGTLVTVSSTSGQAGQHHHHHHGAYP YDVPDYAS [SEQ IDNO: 822]

TABLE 192 ET200-043 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcaccggcagcagcgacagcatagccaacaactatgttcagtggtaccagcagcgcccgggcagtgcccccaccaatgtgatctacgaagatgtccaaagaccctctggggtccctgatcggttctctgggtccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgtctactattgtcagtcttatcatagcgacaatcgttgggtgttcggcggcgggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtggagtctgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtggtggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagccgaggacacggccgtatattactgtgcgcgctctggtgcttactgggactactctgtttacgatgaatggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 823] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTGSSDSIANNYVQWYQQRPGSAPTNVIYEDVQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEAVYYCQSYHSDNRWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSGAYWDYSVYDEWGQGTLVTVSSTSGQAGQHHHHHHGA YPYDVPDYAS [SEQ IDNO: 824]

TABLE 193 ET200-044 DNA Sequencecagtctgtgttgactcagccaccctcagtgtccgtgtccccaggacagacagccaccatcgcctgttctggacataaattgggggataaatatgcttcctggtatcagcagaagtcgggccagtcccctgtgttgatcatctatcaggataataagcggccctcagggattcctgagcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctctggatgaggctgactattattgtcaggcgtgggacagtagtacttatgtggcattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctgcaggagtccggcccaggactggtgaagccttcggagaccctgtccctcacctgcgttgtctctggtggctccatcagcagtagtaactggtggagctgggtccgccagcccccagggaaggggctggagtggattggggaaatctatcatagtgggagccccaactacaacccatccctcaagagtcgagtcaccatatcagtagacaagtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcatgactactcatactttcggttacgatgcttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:825] Amino Acid SequenceQSVLTQPPSVSVSPGQTATIACSGHKLGDKYASWYQQKSGQSPVLIIYQDNKRPSGIPERFSGSNSGNTATLTISGTQALDEADYYCQAWDSSTYVAFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQESGPGLVKPSETLSLTCVVSGGSISSSNWWSWVRQPPGKGLEWIGEIYHSGSPNYNPSLKSRVTISVDKSKNQFSLKLSSVTAADTAVYYCARMTTHTFGYDAWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVPDY AS [SEQ ID NO: 826]

TABLE 194 ET200-045 DNA Sequencecagcctgtgctgactcagccaccctcagtgtcagtggccccaggaaagacggccacgattacttgtgggggaaacaacattggaagtgaaagtgtgcactggtaccaccagaagccaggccaggcccctgtgttggtcatctatgatgatgccggccggccctcagggatccctgagcgattcactggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggacagaaatagtgctcagtttgtcttcggacctgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgcggtgttcatctggattggtggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:827] Amino Acid SequenceQPVLTQPPSVSVAPGKTATITCGGNNIGSESVHWYHQKPGQAPVLVIYDDAGRPSGIPERFTGSNSGNTATLTISRVEAGDEADYYCQVWDRNSAQFVFGPGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGVHLDWWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:828]

TABLE 195 ET200-069 DNA Sequencecagtctgtcgtgacgcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtggttatgtcttcggaactgggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggccgtgtattactgtgcgcgcctgtacgaaggtggttaccatggttggggttcttggctgtcttctgattcttggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 829] Amino Acid SequenceQSVVTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGYVFGTGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLYEGGYHGWGSWLSSDSWGQGTLVTVSSTSGQAGQHHHHH HGAYPYDVPDYAS [SEQID NO: 830]

TABLE 196 ET200-078 DNA Sequencecagtctgtgttgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttattgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgcgcgaaggggcatttgatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 831] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGAFDAFDIWGQGTMVTVSSTSGQAGQHHHHHHGAYPYDV PDYAS [SEQ ID NO:832]

TABLE 197 ET200-079 DNA Sequencetcctatgagctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaattatgtatactggtaccagcagctcccaggaacggcccccaaactcttcatctataggaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctgattattactgtgcagcatgggatgacagcctgagtggttatctcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaatggcgactccaactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 833] Amino Acid SequenceSYELTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLFIYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGYLFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCANGDSNYYYGMDVWGQGTTVTVSSTSGQAGQHHHHHHGA YPYDVPDYAS [SEQ IDNO: 834]

TABLE 198 ET200-081 DNA Sequencecagtctgccctgactcagcctgcctccgtgtccgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacattggtggttataactatgtctcctggtaccaacaacacccaggcaaagcccccaaactcatgatttatgatgtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcatctcatatacacgcacctggaacccctatgtcttcgggagtgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctgggggaggcgtggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccgtcaagctccagggaagggtctggagtgggtctctcttattagtggggatggtggtagcacatactatgcagactctgtgaagggccgattcaccatctccagagacaacagcaaaaactccctgtatctgcaaatgaacagtctgagaactgaggacaccgccttgtattactgtgcaaaagatcgggcagcagctggctactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 835] Amino Acid SequenceQSALTQPASVSGSPGQSITISCTGTSSDIGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCISYTRTWNPYVFGSGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGGGVVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSLISGDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRTEDTALYYCAKDRAAAGYYYYGMDVWGQGTTVTVSSTSGQAGQHHHH HHGAYPYDVPDYAS [SEQID NO: 836]

TABLE 199 ET200-097 DNA Sequencectgcctgtgctgactcagccaccctcagtgtccgtgtccccaggacagacagccatcatcacctgctctggagataaattgggggaaaaatatgtttcctggtatcagcagaagccaggccagtcccctgtactggtcatcgatcaagataccaggaggccctcagggatccctgagcgattctctggctccaactctgggaccacagccactctgaccatcagcgggacccaggctatggatgaggctgactattactgtcaggcgtgggacaggggtgtggtattcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggagacttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttaatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggagtggtaataacataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagatagtatacggtatggcatcacctggggaggttttgactactggggccagggaaccctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 837] Amino Acid SequenceLPVLTQPPSVSVSPGQTAIITCSGDKLGEKYVSWYQQKPGQSPVLVIDQDTRRPSGIPERFSGSNSGTTATLTISGTQAMDEADYYCQAWDRGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGDLVQPGRSLRLSCAASGFTFNDYAMHWVRQAPGKGLEWVSGISWSGNNIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDSIRYGITWGGFDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ IDNO: 838]

TABLE 200 ET200-098 DNA Sequencecagcctgtgctgactcagccaccctcggtgtccaagggcttgagacagaccgccacactcacctgcactgggaacagcaacaatgttggcaacctaggagtagcttggctgcagcagcaccagggccaccctcccaaactcctatcctacaggaataacaaccggccctcagggatctcagagagattatctgcatccaggtcaggaaacacagcctccctgaccattactggactccagcctgaggacgaggctgactattactgctcagcatgggacagtagcctcagtgcttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggagtcgtggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccgtcaagctccggggaagggtctggagtgggtctctcttattaattgggatggtggtagcacctactatgcagactctgtgaagggtcgattcaccatctccagagacaacagcaaaaactccctgtatctgcaaatgaacagtctgagagctgaggacaccgccttgtattactgtgcaaaagggatgggcctgagggcgtttgactactggggccagggaaccctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 839] Amino Acid SequenceQPVLTQPPSVSKGLRQTATLTCTGNSNNVGNLGVAWLQQHQGHPPKLLSYRNNNRPSGISERLSASRSGNTASLTITGLQPEDEADYYCSAWDSSLSAWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGVVVQPGGSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSLINWDGGSTYYADSVKGRFTISRDNSKNSLYLQMNSLRAEDTALYYCAKGMGLRAFDYWGQGTLVTVSSTSGQAGQHHHHHHG AYPYDVPDYAS [SEQ IDNO: 840]

TABLE 201 ET200-099 DNA Sequencecagtctgtgttgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcctgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtccggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcttcatgggatgacagcctgaatggccgttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggggctgaggtgaggaagcctggggcctcagtgaaggtttcctgcaagacttctggatacaccttcagttggtatgctatacattgggtgcgccaggcccccggacaaaggcttgagtggatgggatggatcaacgctggcaatggaaacacaaaatattcacagaaatttcagggcagagtcagtcttaccagggacacatccgcgagcacagcctacatggagctgagcagcctgagatctgatgacacggctgtgtattactgtgcgagacccgataattatggttcgggtggggatgtttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 841] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCASWDDSLNGRYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVRKPGASVKVSCKTSGYTFSWYAIHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVSLTRDTSASTAYMELSSLRSDDTAVYYCARPDNYGSGGDVFDIWGQGTMVTVSSTSGQAGQHHHHHH GAYPYDVPDYAS [SEQID NO: 842]

TABLE 202 ET200-100 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactttgtgcagtggtaccagcagcgcccgggcagtgcccccacccctatgatctatgaggataacaacagaccccctggggtccctgatcggttctctgcctccgtcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgataccagcaatgtggtattcggcggggggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggagggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatgaaatgaactgggtccgccaggctccagggaaggggctggagtgggtttcatacattagtagtagtggtagtaccatatactacgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggctgtttattactgtgcacgctgggactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:843] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNFVQWYQQRPGSAPTPMIYEDNNRPPGVPDRFSASVDSSSNSASLTISGLKTEDEADYYCQSYDTSNVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARWDYGMDVWGQGTTVTVSSTSGQAGQHHHHHHGAYPYDVPD YAS [SEQ ID NO: 844]

TABLE 204 ET200-102 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcaccggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgagtgcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaagtttcctgcaaggcttctggatacaccttcacgaactatgctctgcattgggtgcgccaggcccccggacaagggcttgagtggatggcatggatcaacggtggcaatggtaacacaaaatattcacagaacttccagggcagagtcaccattaccagggacacatccgcgagcacagcctatatggagctgagcagcctgagatctgaagacacggctgtgtattactgtgcgaaaccggaggaaacagctggaacaatccactttgactactggggccagggaaccccggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 847] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTNYALHWVRQAPGQGLEWMAWINGGNGNTKYSQNFQGRVTITRDTSASTAYMELSSLRSEDTAVYYCAKPEETAGTIHFDYWGQGTPVTVSSTSGQAGQHHHHHHG AYPYDVPDYAS [SEQID NO: 848]

TABLE 205 ET200-103 DNA Sequencecaggctgtgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcaccatcacggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgggggagggttactatgatagtagtggttattccaacggtgatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 849] Amino Acid SequenceQAVLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTITVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAGEGYYDSSGYSNGDAFDIWGQGTMVTVSSTSGQAGQHHHHHHG AYPYDVPDYAS [SEQ IDNO: 850]

TABLE 206 ET200-104 DNA Sequenceaattttatgctgactcagccccactctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagcattgccagcaactatgtgcagtggtaccagcagcgcccgggcagtgcccccaccactgtgatctatgaggataaccaaagaccctctggggtccctgatcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgatagcagcaatgtggtattcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggagggtccctgagactctcctgtgcagcctctggattcaccttcagtagttatgaaatgaactgggtccgccaggctccagggaaggggctggagtgggtttcatacattagtagtagtggtagtaccatatactacgcagactctgtgaagggccgattcaccatctccagagacaacgccaagaactcactgtatctgcaaatgaacagcctgagagccgaggacacggctgtttattactgtgcacgctgggactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:851] Amino Acid SequenceNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNVVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARWDYGMDVWGQGTTVTVSSTSGQAGQHHHHHHGAYPYDVPD YAS [SEQ ID NO: 852]

TABLE 207 ET200-105 DNA Sequencetcctatgtgctgactcagccaccctcagtgtccgtgtccccaggacagacagccagcatcacctgctctggagatagattgacgaataaatatgtttcctggtatcaacagaagccaggccagtcccctgtgttggtcatctatgaggatgccaagcggccctcagggatccctgcgcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctatggatgagtctgaatattactgtcaggcgtgggacagcagtgtggtggtttttggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggatttacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagtataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagatgaggacacggccttgtattactgtgcaaaagaccgaggggggggagttatcgttaaggatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 853] Amino Acid SequenceSYVLTQPPSVSVSPGQTASITCSGDRLTNKYVSWYQQKPGQSPVLVIYEDAKRPSGIPARFSGSNSGNTATLTISGTQAMDESEYYCQAWDSSVVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRDEDTALYYCAKDRGGGVIVKDAFDIWGQGTMVTVSSTSGQAGQHHHHHHGAY PYDVPDYAS [SEQ IDNO: 854]

TABLE 208 ET200-106 DNA Sequencetcctatgagctgactcagccacccgcagcgtctgggacccccggacagagagtcaccatctcttgttctgggggcgtctccaacatcgggagtggtgctctaaattggtaccagcaactcccaggaacggcccccaaactcctcatctatagttacaatcagcggccctcaggggtctctgaccgattctctggctccaggtctgccacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcaacctgggatgatagtgtgaatggttgggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctggagctgaggtgaagaagcctggggattcagtgaaggtctcctgcaagccttctggttacaattttctcaactatggtatcaactgggtgcgacaggcccctggacaagggcttgagtggatgggatggattagcacttacaccggtaacacaaactatgcacagaagctgcagggcagagtcaccttcaccacagacacatccacgagcacagcctacatggagatgaggagcctgagatctgacgacacggccgtgtattactgtgcgcgccagcagggtggtggttggtacgatgtttggggtcaaggtactctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 855] Amino Acid SequenceSYELTQPPAASGTPGQRVTISCSGGVSNIGSGALNWYQQLPGTAPKLLIYSYNQRPSGVSDRFSGSRSATSASLAISGLQSEDEADYYCATWDDSVNGWVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGAEVKKPGDSVKVSCKPSGYNFLNYGINWVRQAPGQGLEWMGWISTYTGNTNYAQKLQGRVTFTTDTSTSTAYMEMRSLRSDDTAVYYCARQQGGGWYDVWGQGTLVTVSSTSGQAGQHHHHHHGA YPYDVPDYAS [SEQ IDNO: 856]

TABLE 209 ET200-107 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggagagaaggtcaccatctcctgctctggaagcaacttcaatgttggaaataatgatgtatcctggtatcagcaactcccaggtgcagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctggacatcaccgggctccacagtgacgacgaggccgattattactgcggaacatgggatagcagcctgaatactgggggggtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatactatcagctgggtacgacaggcccctggacaagggcttgagtggatgggatggatcagcacttacaatggtctcacaaactatgcacagaacctccagggcagagtcaccatgactacagacacattcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattactgtgtgagagaggggtcccccgactacggtgacttcgcgtcctttgactactggggccagggaaccctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 857] Amino Acid SequenceQSVVTQPPSVSAAPGEKVTISCSGSNFNVGNNDVSWYQQLPGAAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLDITGLHSDDEADYYCGTWDSSLNTGGVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTISWVRQAPGQGLEWMGWISTYNGLTNYAQNLQGRVTMTTDTFTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFASFDYWGQGTLVTVSSTSGQAGQHHHHH HGAYPYDVPDYAS [SEQID NO: 858]

TABLE 210 ET200-108 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctgcgcccccgggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagttcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggatttctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcgccggactccagactggggacgaggccgattattactgcggaacatgggataccagcctgagtggtttttatgtcttcggaagtgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatactatcagctgggtacgacaggcccctggacaagggcttgagtggatgggatggatcagcacttacaatggtctcacaaactatgcacagaacctccagggcagagtcaccatgactacagacacattcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattactgtgtgagagaggggtcccccgactacggtgacttcgcgtcctttgactactggggccagggaaccctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 859] Amino Acid SequenceQSVLTQPPSVSAPPGQKVTISCSGSSSNIGNNYVSWYQQFPGTAPKLLIYDNNKRPSGISDRFSGSKSGTSATLGIAGLQTGDEADYYCGTWDTSLSGFYVFGSGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTISWVRQAPGQGLEWMGWISTYNGLTNYAQNLQGRVTMTTDTFTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFASFDYWGQGTLVTVSSTSGQAGQHHHHHH GAYPYDVPDYAS [SEQID NO: 860]

TABLE 211 ET200-109 DNA Sequencectgcctgtgctgactcagccaccctcagcgtctgcgacccccgggcagagggtcaccatctcttgttctggaaccacctccaacatcggaagtaatactgtacactggtaccagcagctcccagggacggcccccaaactcctcatctataataataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccggtccgaggatgaggctacatattcctgtgcaacatgggatgacagcctgagtggtgtggtcttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagagatcccgcctacggtgactacgagtatgatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 861] Amino Acid SequenceLPVLTQPPSASATPGQRVTISCSGTTSNIGSNTVHWYQQLPGTAPKLLIYNNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEATYSCATWDDSLSGVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDPAYGDYEYDAFDIWGQGTMVTVSSTSGQAGQHHHHHHGAY PYDVPDYAS [SEQ IDNO: 862]

TABLE 212 ET200-110 DNA Sequencecagtctgtgttgacgcagccgccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaactaatggtgtaaactggttccagcagttcccaggaacggcccccaaactcctcatctatactaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgcggatgaggctgattattactgtgcagtgtgggaccacagcctgaatggtccggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagaggggccggttttgatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 863] Amino Acid SequenceQSVLTQPPSASGTPGQRVTISCSGSSSNIGTNGVNWFQQFPGTAPKLLIYTNDQRPSGVPDRFSGSKSGTSASLAISGLQSADEADYYCAVWDHSLNGPVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGAGFDAFDIWGQGTMVTVSSTSGQAGQHHHHHHGAYPYDV PDYAS [SEQ ID NO:864]

TABLE 213 ET200-111 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgagactgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagaggggctagatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 865] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDETDYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGLDAFDIWGQGTMVTVSSTSGQAGQHHHHHHGAYPYDVPD YAS [SEQ ID NO:866]

TABLE 214 ET200-112 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatgtatagtaatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattattgtgcagcatgggatgacagcctgaatggttatgtcttcgcagctgggacccagctcaccgttttaagttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagaggggctagatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO:867] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLMYSNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFAAGTQLTVLSSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAREGLDAFDIWGQGTMVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:868]

TABLE 215 ET200-113 DNA Sequencecagtctgtcgtgacgcagccgccctcagtgtctgcggccccaggacagaaggtcaccatctcctgctctggaagcagctccaacattgggaataattatgtatcctggtaccagcagctcccaggaacagcccccaaactcctcatttatgacaataataagcgaccctcagggattcctgaccgattctctggctccaagtctggcacgtcagccaccctgggcatcactggactccagactggggacgaggccgattattactgcggaacatgggatagcagcctgagtgctgcttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtccagctggtacagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacagctttaccagctatactatcagctgggttcgacaggcccctggacaaggccttgagtggatgggatgggtcagcacttacaatggtctcagaaactatgcacagaacctccagggcagagtcaccatgactacagacacactcacgaccacagcctacatggagctgaggagcctcagatctgacgacacggccgtgtattattgtgtgagagaggggtcccccgactacggtgacttcgcggcctttgactactggggccagggcaccctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 869] Amino Acid SequenceQSVVTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSSLSAAYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYSFTSYTISWVRQAPGQGLEWMGWVSTYNGLRNYAQNLQGRVTMTTDTLTTTAYMELRSLRSDDTAVYYCVREGSPDYGDFAAFDYWGQGTLVTVSSTSGQAGQHHHHH HGAYPYDVPDYAS [SEQID NO: 870]

TABLE 216 ET200-114 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgagacccccgggcagagggtcaccatctcttgttctggaagcaggtccaacatcggaactaatattgtacactggtaccagcagcgcccaggaatggcccccaaactcctcacttatggtagtcggcggccctcaggggtcccggaccgattctctggctccaagtttggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattattgtgcagcatgggatgacagtctgaatggtccggctttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctacagcagtggggcgcaggactgttgaagccttcggagaccctgtccctcacctgcgctgtctatggtgggtccttcagtggttactactggagctggatccgccagcccccagggaaggggctggagtggattggggaaatcaatcatagtggaagcaccaactacaacccgtccctcaagagtcgagtcaccatatcagtagacacgtccaagaaccagttctccctgaagctgagctctgtgaccgccgcggacacggctgtgtattactgtgcgagagacggtgggggctactttgactactggggccagggaaccctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 871] Amino Acid SequenceQAVLTQPPSASETPGQRVTISCSGSRSNIGTNIVHWYQQRPGMAPKLLTYGSRRPSGVPDRFSGSKFGTSASLAISGLQSEDEADYYCAAWDDSLNGPAFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDGGGYFDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:872]

TABLE 217 ET200-115 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccatctcctgcactgggagcagctccaatatcggggcacgttatgatgtacactggtaccagcaactcccaggaacagccccccgactcctcatctctgctaactacgatcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcactgggctccaggctgaggatgaggctgattattactgccagtcctatgacagcagtgtgagtgcttgggtgttcggcggagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctggggctgaagtgaaggagcctggggcctcagtgaggatctcctgccaggcatctggatacaacttcatcagttattatatgcactgggtgcggcaggcccctgggcaaggtcttgagtggatgggcaccatcaacccaggcagtggtgagacagactactcacagaagttgcagggcagagtcaccatgaccagggacccgtccacgggtacattcgacatggggctgagcagcctgacatctggggacacggccgtctattattgtgcgacaggtctcatcagaggagctagcgatgcttttaatatctggggccgggggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 873] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTISCTGSSSNIGARYDVHWYQQLPGTAPRLLISANYDRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSVSAWVFGGGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKEPGASVRISCQASGYNFISYYMHWVRQAPGQGLEWMGTINPGSGETDYSQKLQGRVTMTRDPSTGTFDMGLSSLTSGDTAVYYCATGLIRGASDAFNIWGRGTMVTVSSTSGQAGQHHHHHHG AYPYDVPDYAS [SEQID NO: 874]

TABLE 218 ET200-116 DNA Sequencecagcctgtgctgactcagccaccctcagtgtccgtgtccccaggacagacggccgccatcccctgttctggagataagttgggggataaatttgcttcctggtatcagcagaagccaggccagtcccctgtgctggtcatctatcaagatactaagcggccctcagggatccctgagcgattctctggctccaactctgggaacacagccactctgaccatcagcgggacccaggctatggatgaggctgactattactgtcagacgtgggccagcggcattgtggtgttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtacagctgcagcagtcaggtccaggactggtgaagccctcgcagaccctctcactcacctgtgccatctccggggacagtgtctctagcaacagtgctgcttggaactggatcaggcagtccccatcgagaggccttgagtggctgggaaggacatactacaggtccaagtggtataatgattatgcagtatctgtgaaaagtcgaataaccatcaacccagacacatccaagaaccagttctccctgcagctgaactctgtgactcccgaggacacggctgtgtattactgtgcaagagagcgcagtggctggaagggatttgactactggggccagggaaccctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 875] Amino Acid SequenceQPVLTQPPSVSVSPGQTAAIPCSGDKLGDKFASWYQQKPGQSPVLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQTWASGIVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCARERSGWKGFDYWGQGTLVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:876]

TABLE 219 ET200-117 DNA Sequencegatgttgtgatgactcagtctccaccctccctgtccgtcacccctggagagccggcctccatcacctgcaggtctagtcagagcctcctggaaagaaatgcatacaactacttggattggtacctgcagaggccaggacagtctccacagctcctgatctacttgggttctaatcgggccgccggggtccctgacaggttcagtggcagtggatcaggcagagattttacactgaaaatcagcagagtggagcctgaggatgttggggtttattactgcatgcaagctctacaagctccgttcactttcggcggagggaccaaggtggagatcaaacgttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctgggggaggcttggtacagcctggggggtccctgagactctcctgtgcagcctctggattcacctttagcagctatgccatgagctgggtccgccaggctccagggaaggggctggagtgggtctcagctattagtggtagtggtggtagcacatactacgcagactccgtgaagggccggttcaccatctccagagacaattccaagaacacgctgtatctgcaaatgaacagcctgagagccgaggacacggccgtatattactgtgcgaaatggggcccgtttcaggatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 877] Amino Acid SequenceDVVMTQSPPSLSVTPGEPASITCRSSQSLLERNAYNYLDWYLQRPGQSPQLLIYLGSNRAAGVPDRFSGSGSGRDFTLKISRVEPEDVGVYYCMQALQAPFTFGGGTKVEIKRSRGGGGSGGGGSGGGGSLEMAEVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKWGPFQDAFDIWGQGTMVTVSSTSGQAGQHHHHHHG AYPYDVPDYAS [SEQ IDNO: 878]

TABLE 220 ET200-118 DNA Sequencecaggctgtgctgactcagcctgcctccgtgtctgggtctcctggacagtcgatcaccatctcctgcactggaaccagcagtgacgttggtggttataactatgtctcctggtaccaacagcacccgggcaaagcccccaaactcatgatttatgaggtcagtaatcggccctcaggggtttctaatcgcttctctggctccaagtctggcaacacggcctccctgaccatctctgggctccaggctgaggacgaggctgattattactgcagctcatatacaagcagcagcaccccttatgtcttcggagcagggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagccaggtggacagcagtggcatcagaccaccactttgactactggggccagggaacgctggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 879] Amino Acid SequenceQAVLTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTPYVFGAGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKARWTAVASDHHFDYWGQGTLVTVSSTSGQAGQHHHHH HGAYPYDVPDYAS [SEQID NO: 880]

TABLE 221 ET200-119 DNA Sequencecaggctgtgcttactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtgcagtctggggctgaggtgaagaagcctgggtcctcggtgaaggtctcctgcaaggcttctggaggcaccttcagcagctatgctatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggagggatcatccctatctttggtacagcaaactacgcacagaagttccagggcagagtcacgattaccgcggacgaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcgagagattgggactacatggacgtctggggcaaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQID NO: 881] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDWDYMDVWGKGTTVTVSSTSGQAGQHHHHHHGAYPYDVP DYAS [SEQ ID NO:882]

TABLE 222 ET200-120 DNA Sequencetcctatgagctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtgcagctggtggagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgagagacctatctcggggagctaacccgcattactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 883] Amino Acid SequenceSYELTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDLSRGANPHYYYYYGMDVWGQGTTVTVSSTSGQAGQH HHHHHGAYPYDVPDYAS[SEQ ID NO: 884]

TABLE 223 ET200-121 DNA Sequencecagtctgtgttgacgcagccgccctcagtgtctggggccccagggcagagggtcaccgtctcctgcactgggagcagatccaacatcggggcaggatatgatgtacactggtaccagcaacttccaggaacagcccccaaactcctcatctatggaaatagtaatcggcctccaggggtccctgaccgattctctgggtctaagtctggcacctcagcctccctggtcatcactgggctccaggctgaggatgccgctgattattactgccagtcctatgacaacactgtgcgtgaatcaccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtacagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggtttccggatacaccctcactgaattatccatgcactgggtgcgacaggctcctggaaaagggcttgagtggatgggaggttttgatcctgaagatggtgaaacaatctacgcacagaagttccagggcagagtcaccatgaccgaggacacatctacagacacagcctacatggagctgagcagcctgagatctgaggacacggccgtgtattactgtgcaacagagagtaatttagtgtcccggcactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 885] Amino Acid SequenceQSVLTQPPSVSGAPGQRVTVSCTGSRSNIGAGYDVHWYQQLPGTAPKLLIYGNSNRPPGVPDRFSGSKSGTSASLVITGLQAEDAADYYCQSYDNTVRESPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATESNLVSRHYYYYGMDVWGQGTTVTVSSTSGQAG QHHHHHHGAYPYDVPDYAS[SEQ ID NO: 886]

TABLE 224 ET200-122 DNA Sequencectgcctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaaccagctccaacatcggaagtaattctgtagactggtaccagcagctcccaggaacggcccccaaactcctcatctatagtaataatcagcggccctcaggggtccctgaccgaatctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctgaatggttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaagtgcagctggtgcagtctggggctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggatacaccttcaccggctactatatgcactgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcaaccctaacagtggtggcacaaactatgcacagaagtttcagggcagggtcaccatgaccagggacacgtccatcagcacagcctacatggagctgagcaggctgagatctgacgacacggccgtgtattactgtgcgagagattacggatactatggttcggggagttattcgagcggccccctttactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 887] Amino Acid SequenceLPVLTQPPSASGTPGQRVTISCSGTSSNIGSNSVDWYQQLPGTAPKLLIYSNNQRPSGVPDRISGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDYGYYGSGSYSSGPLYYYYGMDVWGQGTTVTVSSTSGQAGQHHHHHHGAYPYDVPDYAS [SEQ ID NO: 888]

TABLE 225 ET200-123 DNA Sequencecaggctgtgctgactcagccaccctcagcgtctgggacccccgggcagagggtcaccatctcttgttctggaagcagctccaacatcggaagtaatactgtaaactggtaccagcagctcccaggaacggcccccaaactcctcatgtataataatgatcagcggccctcaggggtccctgaccgattctctggctccaagtctggcacctcagcctccctggccatcagtgggctccagtctgaggatgaggctgattattactgtgcagcatgggatgacagcctcaatggttatgtcttcggacctgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtggagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccagctatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacagaagctccagggcagagtcaccatgaccacagacacatccacgagcacagcctacatggagctgaggagcctgagatctgacgacacggccgtgtattactgtgcgagagacctatctcggggagctaacccgcattactactactactacggtatggacgtctggggccaagggaccacggtcaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ ID NO: 889] Amino Acid SequenceQAVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLMYNNDQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGYVFGPGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDLSRGANPHYYYYYGMDVWGQGTTVTVSSTSGQAG QHHHHHHGAYPYDVPDYAS[SEQ ID NO: 890]

TABLE 226 ET200-125 DNA Sequenceaattttatgctgactcagccccacgctgtgtcggagtctccggggaagacggtaaccatctcctgcacccgcagcagtggcagtattgccagcaactatgtgcagtggtaccagcagcgcccgggcagttccccccgcactgtgatttatgaggataatcaaagaccctctggggtccctggtcggttctctggctccatcgacagctcctccaactctgcctccctcaccatctctggactgaagactgaggacgaggctgactactactgtcagtcttatgattccaccagtgtgcttttcggcggagggaccaagctgaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggccgaggtccagctggtgcagtctggggctgaggtgaagaagccagggtcctcggtgaaggtctcctgcaaggcctcgggaggcaccttcagcagcaattctctcagctgggtgcgacaggcccctggacaagggcttgagtggatgggaaggatcttccctatcctgggtataacaaactatgcacagaagttccagggcagagtcacgattaccgcggacaaatccacgagcacagcctacatggagctgagcagcctgagatctgaggacacggccgtctattactgtgcgagaggaaactaccaatggtatgatgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 891] Amino Acid SequenceNFMLTQPHAVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSSPRTVIYEDNQRPSGVPGRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSTSVLFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAEVQLVQSGAEVKKPGSSVKVSCKASGGTFSSNSLSWVRQAPGQGLEWMGRIFPILGITNYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARGNYQWYDAFDIWGQGTMVTVSSTSGQAGQHHHHHHGAYPY DVPDYAS [SEQ ID NO:892]

TABLE 227 ET200-005 DNA Sequencecagcctgtgctgactcagccaccctcagtgtcagtggtcccaggaaagacggccaggattacctgtgggggaaaaaacattggaagtaaaagtgtgcactggtaccagcagaagccaggccaggcccctgtggtggtcatccattatgatagtgaccggccctcagggatccctgagcgattctctggctccaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaggtgtgggatagtagtagtgatcatccttatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtgcagtctggagctgaggtgaagaagcctggggcctcagtgaaggtctcctgcaaggcttctggttacacctttaccaactatggtatcagctgggtgcgacaggcccctggacaagggcttgagtggatgggatggatcagcgcttacaatggtaacacaaactatgcacataagctccagggcagagtcaccatgaccacagacacatccacgagcacagccaacatggagctgaggagcctgagacctgacgacactgccgtgtattactgtgcgcgctcttacttcggttctcatgattactggggtcaaggtactctggtgaccgtctcctcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct [SEQ IDNO: 893] Amino Acid SequenceQPVLTQPPSVSVVPGKTARITCGGKNIGSKSVHWYQQKPGQAPVVVIHYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHPYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGISWVRQAPGQGLEWMGWISAYNGNTNYAHKLQGRVTMTTDTSTSTANMELRSLRPDDTAVYYCARSYFGSHDYWGQGTLVTVSSTSGQAGQHHHHHHGAYP YDVPDYAS [SEQ IDNO: 894]

TABLE 228 ET200-124 DNA Sequencetcctatgtgctgactcagccaccctcggtgtcagtggccccaggaaagacggccaggatttcctgtgggggaaacgacattggaagtaaaagtgttttctggtatcagcagaggccaggccaggcccctgtgttggtcgtctatgatgatagcgaccggccctcagggctccctgagcgattctctggcttcaactctgggaacacggccaccctgaccatcagcagggtcgaagccggggatgaggccgactattactgtcaagtgtgggatagtagtagtgatcattatgtcttcggaactgggaccaaggtcaccgtcctaggttctagaggtggtggtggtagcggcggcggcggctctggtggtggtggatccctcgagatggcccaggtgcagctggtggagtctgggggaggcttggtacagcctggcaggtccctgagactctcctgtgcagcctctggattcacctttgatgattatgccatgcactgggtccggcaagctccagggaagggcctggagtgggtctcaggtattagttggaatagtggtagcataggctatgcggactctgtgaagggccgattcaccatctccagagacaacgccaagaactccctgtatctgcaaatgaacagtctgagagctgaggacacggccttgtattactgtgcaaaagatataacctatggttcggggagttatggtgcttttgatatctggggccaagggacaatggtcaccgtctcttcaactagtggccaggccggccagcaccatcaccatcaccatggcgcatacccgtacgacgttccggactacgcttct[SEQ ID NO: 895] Amino Acid SequenceSYVLTQPPSVSVAPGKTARISCGGNDIGSKSVFWYQQRPGQAPVLVVYDDSDRPSGLPERFSGFNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKVTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTALYYCAKDITYGSGSYGAFDIWGQGTMVTVSSTSGQAGQHHHHHHG AYPYDVPDYAS [SEQID NO: 896]

XIII. CDR Sequences of Exemplary Extracellular Antigen-Binding Domains(e.g., scFvs)

TABLE 229 Antibody V_(H)CDR1 V_(H)CDR2 V_(H)CDR3 ET200-001 GGSFSGYYINHSGST AREGPYDGFDS [SEQ ID NO: 309] [SEQ ID NO: 310] [SEQ ID NO: 311]ET200-002 GYPFNKYD IIPIFRTT AREWFYWDI [SEQ ID NO: 315] [SEQ ID NO: 316][SEQ ID NO: 317] ET200-003 GFTFSSYG ISHDGSNK ARSNQWSGYFSFDY [SEQ ID NO:321] [SEQ ID NO: 322] [SEQ ID NO: 323] ET200-005 GYTFTNYG ISAYNGNTARSYFGSHDY [SEQ ID NO: 326] [SEQ ID NO: 327] [SEQ ID NO: 328] ET200-006GYTFTTYG INTYNGHT ARVIYGSGDY [SEQ ID NO: 332] [SEQ ID NO: 333] [SEQ IDNO: 334] ET200-007 GYSISSGYF IYHSRST ARGYGYFDY [SEQ ID NO: 335] [SEQ IDNO: 336] [SEQ ID NO: 337] ET200-008 GFTFGDYG INWNGGST ARSKYNFHVYYDY [SEQID NO: 340] [SEQ ID NO: 341] [SEQ ID NO: 342] ET200-009 GYTFTSYGISAYNGNT ARSSGNMVSWKDM [SEQ ID NO: 346] [SEQ ID NO: 327] [SEQ ID NO:347] ET200-010 GYTFTSYG ISAYNGNT ARGAVAYHD [SEQ ID NO: 346] [SEQ ID NO:327] [SEQ ID NO: 351] ET200-011 GGTLSSYA IIPMFGTA ARGVHYASFDH [SEQ IDNO: 354] [SEQ ID NO: 355] [SEQ ID NO: 356] ET200-012 GFPFNIFG ISGYNGNTARGAYGGMDT [SEQ ID NO: 360] [SEQ ID NO: 361] [SEQ ID NO: 362] ET200-013GYMFTSYG ISANNGKT ARHIGGSYFDR [SEQ ID NO: 366] [SEQ ID NO: 367] [SEQ IDNO: 368] ET200-014 GFTFSSYA ISGSDGST ARSHEANLVGDW [SEQ ID NO: 372] [SEQID NO: 373] [SEQ ID NO: 374] ET200-015 GYTFTSYG ISAYNGNT ARWGGFGAVDH[SEQ ID NO: 346] [SEQ ID NO: 327] [SEQ ID NO: 376] ET200-016 GFTFSSYSISSSSSYI ARGQGYDY [SEQ ID NO: 378] [SEQ ID NO: 379] [SEQ ID NO: 380]ET200-017 GGSFSGYY INHSGST ARYYPGMDM [SEQ ID NO: 309] [SEQ ID NO: 310][SEQ ID NO: 384] ET200-018 GYTLNELS FDPEDGET ARGGYGDS [SEQ ID NO: 387][SEQ ID NO: 388] [SEQ ID NO: 389] ET200-019 GGTFSSDA TIPMFGTAAREGYYYPSAYLGSVLNDIS [SEQ ID NO: 393] [SEQ ID NO: 355] SVYDE [SEQ ID NO:394] ET200-020 GYTFTSYG ISAYNGNT ARSMTSFDY [SEQ ID NO: 346] [SEQ ID NO:327] [SEQ ID NO: 396] ET200-021 GYTFTSYG ISAYNGNT ARSVYDLDT [SEQ ID NO:346] [SEQ ID NO: 327] [SEQ ID NO: 400] ET200-022 GFTFDDYA ISWNSGSIARYRQVGSAYDS [SEQ ID NO: 403] [SEQ ID NO: 404] [SEQ ID NO: 405]ET200-023 GYTFTSYG ISAYNGNT ARYWGFGVSDR [SEQ ID NO: 346] [SEQ ID NO:327] [SEQ ID NO: 408] ET200-024 GGTFSSYA IIPIFGTA ARYNYYYYDS [SEQ ID NO:411] [SEQ ID NO: 412] [SEQ ID NO: 413] ET200-025 GGTFSSYA IIPIFGTAARYWGYDSYDE [SEQ ID NO: 411] [SEQ ID NO: 412] [SEQ ID NO: 415] ET200-026GGTFSSYA IIPIFGTA ARNNHYYNDY [SEQ ID NO: 411] [SEQ ID NO: 412] [SEQ IDNO: 349] ET200-027 GYTFTDYY VDPEDGET ARYWSYSFDYLYMPEGNDW [SEQ ID NO:420] [SEQ ID NO: 421] [SEQ ID NO: 422] ET200-028 GYNFLNYG ISTYTGNTARDLYYYEGVDY [SEQ ID NO: 425] [SEQ ID NO: 426] [SEQ ID NO: 427]ET200-029 GFTFSSYA ISYDGSNK ARSYFTSGFYDY [SEQ ID NO: 372] [SEQ ID NO:431] [SEQ ID NO: 432] ET200-030 GYTLTELS FDPEDGET ARMSSMYYD [SEQ ID NO:436] [SEQ ID NO: 388] [SEQ ID NO: 437] ET200-031 GFTVSDYY ISGSGNSIARSTKFDY [SEQ ID NO: 440] [SEQ ID NO: 441] [SEQ ID NO: 442] ET200-032GYSFTNYW IYPGDSDT ARSTGSSHMSDE [SEQ ID NO: 444] [SEQ ID NO: 445] [SEQ IDNO: 446] ET200-033 GGSFSGYY ITHSGRS ARSSIMSDY [SEQ ID NO: 309] [SEQ IDNO: 450] [SEQ ID NO: 451] ET200-034 GGTFSSYA IIPIFGTA ARGSALDHYDR [SEQID NO: 411] [SEQ ID NO: 412] [SEQ ID NO: 453] ET200-035 GGTFSSYAIIPIFGTA ARYNYYFNDY [SEQ ID NO: 411] [SEQ ID NO: 412] [SEQ ID NO: 456]ET200-037 GYTFTSYG ISAYNGNT ARSMFGAHDS [SEQ ID NO: 346] [SEQ ID NO: 327][SEQ ID NO: 458] ET200-038 GGTFSSYA IIPIFGTA ARGASFDRHDN [SEQ ID NO:411] [SEQ ID NO: 412] [SEQ ID NO: 459] ET200-039 GGTFSSYA IIPIFGTAARSNYYYNDY [SEQ ID NO: 411] [SEQ ID NO: 412] [SEQ ID NO: 453] ET200-040GYTLTELS FDPEDGET ARYSGVYYD [SEQ ID NO: 436] [SEQ ID NO: 388] [SEQ IDNO: 464] ET200-041 GGTFSSYA MNPNSGNT ARYYSYGYD [SEQ ID NO: 411] [SEQ IDNO: 466] [SEQ ID NO: 467] ET200-042 GDSVSTNSVA TYYRSKWSN ARSSSWYQIFDY[SEQ ID NO: 471] [SEQ ID NO: 472] [SEQ ID NO: 473] ET200-043 GFTFSSYAISGSGGST ARSGAYWDYSVYDE [SEQ ID NO: 372] [SEQ ID NO: 475] [SEQ ID NO:476] ET200-044 GGSISSSNW IYHSGSP ARMTTHTFGYDA [SEQ ID NO: 480] [SEQ IDNO: 481] [SEQ ID NO: 482] ET200-045 GYTFTSYG ISAYNGNT ARGVHLDW [SEQ IDNO: 346] [SEQ ID NO: 327] [SEQ ID NO: 486] ET200-069 GGSFSGYY INHSGSTARLYEGGYHGWGSWLSSDS [SEQ ID NO: 309] [SEQ ID NO: 310] [SEQ ID NO: 489]ET200-078 GGSFSGYY INHSGST AREGAFDAFDI [SEQ ID NO: 309] [SEQ ID NO: 310][SEQ ID NO: 492] ET200-079 GFTFDDYA ISWNSGSI ANGDSNYYYGMDV [SEQ ID NO:403] [SEQ ID NO: 404] [SEQ ID NO: 494] ET200-081 GFTFDDYA ISGDGGSTAKDRAAAGYYYYGMDV [SEQ ID NO: 403] [SEQ ID NO: 496] [SEQ ID NO: 497]ET200-097 GFTFNDYA ISWSGNNI AKDSIRYGITWGGFDY [SEQ ID NO: 500] [SEQ IDNO: 501] [SEQ ID NO: 502] ET200-098 GFTFDDYA INWDGGST AKGMGLRAFDY [SEQID NO: 403] [SEQ ID NO: 506] [SEQ ID NO: 507] ET200-099 GYTFSWYAINAGNGNT ARPDNYGSGGDVFDI [SEQ ID NO: 510] [SEQ ID NO: 511] [SEQ ID NO:512] ET200-100 GFTFSSYE ISSSGSTI ARWDYGMDV [SEQ ID NO: 515] [SEQ ID NO:516] [SEQ ID NO: 517] ET200-101 GYTFTWYA INAGSGNT ARPNNYGSGGDVFDI [SEQID NO: 520] [SEQ ID NO: 521] [SEQ ID NO: 522] ET200-102 GYTFTNYAINGGNGNT AKPEETAGTIHFDY [SEQ ID NO: 525] [SEQ ID NO: 526] [SEQ ID NO:527] ET200-103 GGTFSSYA IIPIFGTA AGEGYYDSSGYSNGDAFDI [SEQ ID NO: 411][SEQ ID NO: 412] [SEQ ID NO: 529] ET200-104 GFTFSSYE ISSSGSTI ARWDYGMDV[SEQ ID NO: 515] [SEQ ID NO: 516] [SEQ ID NO: 517] ET200-105 GFTFDDYAISWNSGSI AKDRGGGVIVKDAFDI [SEQ ID NO: 403] [SEQ ID NO: 404] [SEQ ID NO:532] ET200-106 GYNFLNYG ISTYTGNT ARQQGGGWYDV [SEQ ID NO: 425] [SEQ IDNO: 426] [SEQ ID NO: 536] ET200-107 GYTFTSYT ISTYNGLT VREGSPDYGDFASFDY[SEQ ID NO: 537] [SEQ ID NO: 538] [SEQ ID NO: 539] ET200-108 GYTFTSYTISTYNGLT VREGSPDYGDFASFDY [SEQ ID NO: 537] [SEQ ID NO: 538] [SEQ ID NO:539] ET200-109 GGTFSSYA IIPIFGTA ARDPAYGDYEYDAFDI [SEQ ID NO: 411] [SEQID NO: 412] [SEQ ID NO: 543] ET200-110 GGTFSSYA IIPIFGTA ARGAGFDAFDI[SEQ ID NO: 411] [SEQ ID NO: 412] [SEQ ID NO: 546] ET200-111 GGSFSGYYINHSGST AREGLDAFDI [SEQ ID NO: 309] [SEQ ID NO: 310] [SEQ ID NO: 550]ET200-112 GGSFSGYY INHSGST AREGLDAFDI [SEQ ID NO: 309] [SEQ ID NO: 310][SEQ ID NO: 550] ET200-113 GYSFTSYT VSTYNGLR VREGSPDYGDFAAFDY [SEQ IDNO: 551] [SEQ ID NO: 552] [SEQ ID NO: 553] ET200-114 GGSFSGYY INHSGSTARDGGGYFDY [SEQ ID NO: 309] [SEQ ID NO: 310] [SEQ ID NO: 555] ET200-115GYNFISYY INPGSGET ATGLIRGASDAFNI [SEQ ID NO: 559] [SEQ ID NO: 560] [SEQID NO: 561] ET200-116 GDSVSSNSAA TYYRSKWYN ARERSGWKGFDY [SEQ ID NO: 565][SEQ ID NO: 566] [SEQ ID NO: 567] ET200-117 GFTFSSYA ISGSGGSTAKWGPFQDAFDI [SEQ ID NO: 372] [SEQ ID NO: 475] [SEQ ID NO: 570]ET200-118 GFTFDDYA ISWNSGSI AKARWTAVASDHHFDY [SEQ ID NO: 403] [SEQ IDNO: 404] [SEQ ID NO: 574] ET200-119 GGTFSSYA IIPIFGTA ARDWDYMDV [SEQ IDNO: 411] [SEQ ID NO: 412] [SEQ ID NO: 577] ET200-120 GYTFTSYG ISAYNGNTARDLSRGANPHYYYYYGMDV [SEQ ID NO: 346] [SEQ ID NO: 327] [SEQ ID NO: 578]ET200-121 GYTLTELS FDPEDGET ATESNLSRHYYYYGMDV [SEQ ID NO: 436] [SEQ IDNO: 388] [SEQ ID NO: 579] ET200-122 GYTFTGYY INPNSGGTARDYGYYGSGSYSSGPLYYY [SEQ ID NO: 582] [SEQ ID NO: 583] YGMDV [SEQ ID NO:584] ET200-123 GYTFTSYG ISAYNGNT ARDLSRGANPHYYYYYGMDV [SEQ ID NO: 346][SEQ ID NO: 327] [SEQ ID NO: 578] ET200-124 GFTFDDYA ISWNSGSIAKDITYGSGSYGAFDI [SEQ ID NO: 403] [SEQ ID NO: 404] [SEQ ID NO: 587]ET200-125 GGTFSSNS IFPILGIT ARGNYQWYDAFDI [SEQ ID NO: 589] [SEQ ID NO:590] [SEQ ID NO: 591] Antibody V_(L)CDR1 V_(L)CDR2 V_(L)CDR3 ET200-001SSNIGSNT SNN AAWDDSLNGYV [SEQ ID NO: 312] [SEQ ID NO: 313] [SEQ ID NO:314] ET200-002 SGSIASNY EDN QSYDSSNSVV [SEQ ID NO: 318] [SEQ ID NO: 319][SEQ ID NO: 320] ET200-003 KLGTKY EDN QAWDSDTFVV [SEQ ID NO: 324] [SEQID NO: 319] [SEQ ID NO: 325] ET200-005 NIGSKS YDS QVWDSSSDHPYV [SEQ IDNO: 329] [SEQ ID NO: 330] [SEQ ID NO: 331] ET200-006 NIGSKS YDSQVWDSSSDHPYV [SEQ ID NO: 329] [SEQ ID NO: 330] [SEQ ID NO: 331]ET200-007 NIGSKT YDS QVWDSSSDHRV [SEQ ID NO: 338] [SEQ ID NO: 330] [SEQID NO: 339] ET200-008 SSDVGGYNY DVS SSYTSSSTSKV [SEQ ID NO: 343] [SEQ IDNO: 344] [SEQ ID NO: 345] ET200-009 NSNIGSNY RNN AAWDDSLSAYV [SEQ ID NO:348] [SEQ ID NO: 349] [SEQ ID NO: 350] ET200-010 SSDVGGYNS DVSSSYTSSSTPLV [SEQ ID NO: 352] [SEQ ID NO: 344] [SEQ ID NO: 353] ET200-011SSNISIYD GNN GTWDDSLSGGV [SEQ ID NO: 357] [SEQ ID NO: 358] [SEQ ID NO:359] ET200-012 DSNIGNNY DVK GTWDSRLDAYV [SEQ ID NO: 363] [SEQ ID NO:364] [SEQ ID NO: 365] ET200-013 TSNIGAGYD TNN GTWDSSLSAVV [SEQ ID NO:369] [SEQ ID NO: 370] [SEQ ID NO: 371] ET200-014 NIGSKS YDS QVWDSSSDHYV[SEQ ID NO: 329] [SEQ ID NO: 330] [SEQ ID NO: 375] ET200-015 NIGSKS YDSQVWSDSSSDVV [SEQ ID NO: 329] [SEQ ID NO: 330] [SEQ ID NO: 377] ET200-016SLTDYH ATN NSRDSGTDEVL [SEQ ID NO: 381] [SEQ ID NO: 382] [SEQ ID NO:383] ET200-017 NIGSKS DDS QVWDSSSDHTV [SEQ ID NO: 329] [SEQ ID NO: 385][SEQ ID NO: 386] ET200-018 SSNIGRNG NDN AAWDDSLHGVV [SEQ ID NO: 390][SEQ ID NO: 391] [SEQ ID NO: 392] ET200-019 SGSIASNY EDN QSYDSSNSWV [SEQID NO: 318] [SEQ ID NO: 319] [SEQ ID NO: 395] ET200-020 TSNIGNND DNNGTWDSSVSAS [SEQ ID NO: 397] [SEQ ID NO: 398] [SEQ ID NO: 399] ET200-021NSNIGNNY DNN GTWNTTVTPGYV [SEQ ID NO: 401] [SEQ ID NO: 398] [SEQ ID NO:402] ET200-022 SSNIGNNY DNN GTWDSSLGAPYV [SEQ ID NO: 406] [SEQ ID NO:398] [SEQ ID NO: 407] ET200-023 NIGSKS ADS QVWDSSSYHNYV [SEQ ID NO: 329][SEQ ID NO: 409] [SEQ ID NO: 410] ET200-024 SGSIASNY EDN QSYDSSNLWV [SEQID NO: 318] [SEQ ID NO: 319] [SEQ ID NO: 414] ET200-025 QSISSY AASQQSYSTPFT [SEQ ID NO: 416] [SEQ ID NO: 417] [SEQ ID NO: 418] ET200-026SGSIASNY EDN QSYDSSNWV [SEQ ID NO: 318] [SEQ ID NO: 319] [SEQ ID NO:419] ET200-027 SSNIGAGYD GNN QSYDSSLSDVV [SEQ ID NO: 423] [SEQ ID NO:358] [SEQ ID NO: 424] ET200-028 VSNIGSGA SYS ATWDDSVNG [SEQ ID NO: 428][SEQ ID NO: 429] [SEQ ID NO: 430] ET200-029 NIGSES YDT QVWDSSRDHVV [SEQID NO: 433] [SEQ ID NO: 434] [SEQ ID NO: 435] ET200-030 SSNIGAGYD GNSQSYDSSLSGSYV [SEQ ID NO: 423] [SEQ ID NO: 438] [SEQ ID NO: 439]ET200-031 NIGSKS YDS QVWDSSSDYV [SEQ ID NO: 329] [SEQ ID NO: 330] [SEQID NO: 443] ET200-032 SSNVGSYT NNN AAWDDRLGGYV [SEQ ID NO: 447] [SEQ IDNO: 448] [SEQ ID NO: 449] ET200-033 SGSIASNY EDN QSYDSSNHWV [SEQ ID NO:318] [SEQ ID NO: 319] [SEQ ID NO: 452] ET200-034 TSNIGAGYD NNRGTWDGSLTGAV [SEQ ID NO: 369] [SEQ ID NO: 454] [SEQ ID NO: 455] ET200-035SGSIASNY EDN QSYDSTNWV [SEQ ID NO: 318] [SEQ ID NO: 319] [SEQ ID NO:457] ET200-037 NIGSKS YDS QVWDSSSDHPYV [SEQ ID NO: 329] [SEQ ID NO: 330][SEQ ID NO: 331] ET200-038 SSNIGAGFD ANS QSYDSSLSGVV [SEQ ID NO: 460][SEQ ID NO: 461] [SEQ ID NO: 462] ET200-039 SGSIASNY EDN QSYDSSNWV [SEQID NO: 318] [SEQ ID NO: 319] [SEQ ID NO: 419] ET200-040 SSNIGAGYD GNSQSYDSSLSGYV [SEQ ID NO: 423] [SEQ ID NO: 438] [SEQ ID NO: 465] ET200-041SGSIADNF NDD QSYDNNNRGV [SEQ ID NO: 468] [SEQ ID NO: 469] [SEQ ID NO:470] ET200-042 SSNIGTGYF GNN QSYDSSLSGYV [SEQ ID NO: 474] [SEQ ID NO:358] [SEQ ID NO: 465] ET200-043 SDSIANNY EDV QSYHSDNRWV [SEQ ID NO: 477][SEQ ID NO: 478] [SEQ ID NO: 479] ET200-044 KLGDKY QDN QAWDSSTYVA [SEQID NO: 483] [SEQ ID NO: 484] [SEQ ID NO: 485] ET200-045 NIGSES DDAQVWDRNSAQFV [SEQ ID NO: 433] [SEQ ID NO: 487] [SEQ ID NO: 488] ET200-069SSNIGSNY SNN AAWDDSLSGYV [SEQ ID NO: 490] [SEQ ID NO: 313] [SEQ ID NO:491] ET200-078 SSNIGSNT SNN AAWDDSLNGY [SEQ ID NO: 312] [SEQ ID NO: 313][SEQ ID NO: 493] ET200-079 SSNIGSNY RNN AAWDDSLSGYL [SEQ ID NO: 490][SEQ ID NO: 349] [SEQ ID NO: 495] ET200-081 SSDIGGYNY DVS ISYTRTWNPYV[SEQ ID NO: 498] [SEQ ID NO: 344] [SEQ ID NO: 499] ET200-097 KLGEKY QDTQAWDRGVV [SEQ ID NO: 503] [SEQ ID NO: 504] [SEQ ID NO: 505] ET200-098SNNVGNLG RNN SAWDSSLSA [SEQ ID NO: 508] [SEQ ID NO: 349] [SEQ ID NO:509] ET200-099 SSNIGSNT SND ASWDDSLNGRYV [SEQ ID NO: 312] [SEQ ID NO:513] [SEQ ID NO: 514] ET200-100 SGSIASNF EDN QSYDTSNVV [SEQ ID NO: 518][SEQ ID NO: 319] [SEQ ID NO: 519] ET200-101 NSNIGSNY SSS ATWDDSLNA [SEQID NO: 348] [SEQ ID NO: 523] [SEQ ID NO: 524] ET200-102 SSNIGNNY DNNGTWDSSLSAYV [SEQ ID NO: 406] [SEQ ID NO: 398] [SEQ ID NO: 528] ET200-103SGSIASNY EDN QSYDSTITV [SEQ ID NO: 318] [SEQ ID NO: 319] [SEQ ID NO:530] ET200-104 SGSIASNY EDN QSYDSSNVV [SEQ ID NO: 318] [SEQ ID NO: 319][SEQ ID NO: 531] ET200-105 RLTNKY EDA QAWDSSVVV [SEQ ID NO: 533] [SEQ IDNO: 534] [SEQ ID NO: 535] ET200-106 VSNIGSGA SYN ATWDDSVNG [SEQ ID NO:428] [SEQ ID NO: 429] [SEQ ID NO: 430] ET200-107 NFNVGNND DNNGTWDSSLNTGGV [SEQ ID NO: 540] [SEQ ID NO: 398] [SEQ ID NO: 541]ET200-108 SSNIGNNY DNN GTWDTSLSGFYV [SEQ ID NO: 406] [SEQ ID NO: 398][SEQ ID NO: 542] ET200-109 TSNIGSNT NNN ATWDDSLSGVV [SEQ ID NO: 544][SEQ ID NO: 448] [SEQ ID NO: 545] ET200-110 SSNIGTNG TND AVWDHSLNGPV[SEQ ID NO: 547] [SEQ ID NO: 548] [SEQ ID NO: 549] ET200-111 SSNIGSNTSNN AAWDDSLNGYV [SEQ ID NO: 312] [SEQ ID NO: 313] [SEQ ID NO: 314]ET200-112 SSNIGSNT SND AAWDDSLNGYV [SEQ ID NO: 312] [SEQ ID NO: 513][SEQ ID NO: 314] ET200-113 SSNIGNNY DNN GTWDSSLSAAYV [SEQ ID NO: 406][SEQ ID NO: 398] [SEQ ID NO: 554] ET200-114 RSNIGTNI GS AAWDDSLNGPA [SEQID NO: 556] [SEQ ID NO: 557] [SEQ ID NO: 558] ET200-115 SSNIGARYD ANYQSYDSSVSAWV [SEQ ID NO: 562] [SEQ ID NO: 563] [SEQ ID NO: 564] ET200-116KLGDKF QDT QTWASGIVV [SEQ ID NO: 568] [SEQ ID NO: 504] [SEQ ID NO: 569]ET200-117 QSLLERNAYNY LGS MQALQAPFT [SEQ ID NO: 571] [SEQ ID NO: 572][SEQ ID NO: 573] ET200-118 SSDVGGYNY EVS SSYTSSSTPYV [SEQ ID NO: 343][SEQ ID NO: 575] [SEQ ID NO: 576] ET200-119 SSNIGSNT SNN AAWDDSLNGYV[SEQ ID NO: 312] [SEQ ID NO: 313] [SEQ ID NO: 314] ET200-120 SSNIGSNTSNN AAWDDSLNGYV [SEQ ID NO: 312] [SEQ ID NO: 313] [SEQ ID NO: 314]ET200-121 RSNIGAGYD GNS QSYDNTVRESPYV [SEQ ID NO: 580] [SEQ ID NO: 436][SEQ ID NO: 581] ET200-122 SSNIGSNS SNN AAWDDSLNGYV [SEQ ID NO: 585][SEQ ID NO: 313] [SEQ ID NO: 314] ET200-123 SSNIGSNT NND AAWDDSLNGYV[SEQ ID NO: 312] [SEQ ID NO: 586] [SEQ ID NO: 314] ET200-124 DIGSKS DDSQVWDSSSDHYV [SEQ ID NO: 588] [SEQ ID NO: 385] [SEQ ID NO: 375] ET200-125SGSIASNY EDN QSYDSTSVL [SEQ ID NO: 318] [SEQ ID NO: 319] [SEQ ID NO:592]

TABLE 230 CDR CDR SEQUENCE SEQ ID NO V_(H)CDR1 IFGLH SEQ ID NO: 923V_(H)CDR2 YISGDSNTIYYADTVKG SEQ ID NO: 924 V_(H)CDR3 NSYYALDY SEQ ID NO:925 V_(L)CDR1 RASSSVSSSYLH SEQ ID NO: 926 V_(L)CDR2 STSNLAS SEQ ID NO:927 V_(L)CDR3 QQYSGYPWT SEQ ID NO: 928 V_(H)CDR1 SFGMH SEQ ID NO: 929V_(H)CDR2 YISSGSNNIYFADTVKG SEQ ID NO: 930 V_(H)CDR3 SEYYGSSHMDY SEQ IDNO: 931 V_(L)CDR1 KASQNVGTNVA SEQ ID NO: 932 V_(L)CDR2 SATYRNS SEQ IDNO: 933 V_(L)CDR3 QQYNRYPYT SEQ ID NO: 934

EXAMPLES

The practice of the present invention employs, unless otherwiseindicated, conventional techniques of molecular biology (includingrecombinant techniques), microbiology, cell biology, biochemistry andimmunology, which are well within the purview of the skilled artisan.Such techniques are explained fully in the literature, such as,“Molecular Cloning: A Laboratory Manual”, second edition (Sambrook,1989); “Oligonucleotide Synthesis” (Gait, 1984); “Animal Cell Culture”(Freshney, 1987); “Methods in Enzymology” “Handbook of ExperimentalImmunology” (Weir, 1996); “Gene Transfer Vectors for Mammalian Cells”(Miller and Calos, 1987); “Current Protocols in Molecular Biology”(Ausubel, 1987); “PCR: The Polymerase Chain Reaction”, (Mullis, 1994);“Current Protocols in Immunology” (Coligan, 1991). These techniques areapplicable to the production of the polynucleotides and polypeptides ofthe invention, and, as such, may be considered in making and practicingthe invention. Particularly useful techniques for particular embodimentswill be discussed in the sections that follow.

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how tomake and use the assay, screening, and therapeutic methods of theinvention, and are not intended to limit the scope of what the inventorsregard as their invention.

Example 1—FcRL5 Expression in Various Tissues

The expression of human FcRL5 was assessed and evaluated in varioustissues. As shown in FIG. 1, human FcRL5 was highly expressed inlymphoma and multiple myeloma, but not in other tissues. Top panel ofFIG. 1 shows differential expression of human FcRL5 in tumor cell linesfrom the Cancer Cell Line Encyclopedia (CCLE). The bottom panel of FIG.1 shows differential expression of human FcRL5 in normal tissue fromBioGPS. As shown in FIG. 1, human FcRL5 expression is limited to MM andlymphoma compared to other malignant cells. Normal expression appearedlimited to B-cells and plasma cells. Potential FcRL5 targeted CAR T celleradication of these normal cell types may not have significant adverseeffects based on inventors' patient experience with CD19 targeted CAR Tcells. Any lack of physiologic antibody production can be addressed withintravenous immunoglobulin treatment.

Example 2—Selection of ScFv Specific for FcRL5 Using a Fully Human PhageDisplay Library

Phage display selection against FcRL5 was conducted using a cell panningstrategy with 31 human scFv naïve and semi-synthetic phagesub-libraries. FcRL5 overexpressing 3T3 cells were used in positivepanning, FcRL1, 2, 3, 4 and 6 overexpressing 3T3 cells (5 cell lines intotal) were used in negative panning (FIG. 2). Bound clones were theneluted and used to infect E. Coli XL1-Blue. The scFv phage clonesexpressed in the bacteria were purified as previously described(Yasmina, et al. Probing the binding mechanism and affinity oftanezumab, a recombinant humanized anti-NGF monoclonal antibody, using arepertoire of biosensors. Protein Science 2008, 17(8):1326-1335;Roberts, et al. Vaccination with CD20 peptides induces a biologicallyactive, specific immune response in mice. Blood 2002, 99(10):3748-3755).Panning was performed for about 3 to about 4 cycles to enrich scFv phageclones that bind to FcRL5 specifically. Positive clones were determinedby an ELISA method against His-tag FcRL5.

Positive clones were further tested for their binding to FcRL5 on livecell surfaces by flow cytometry, using FcRL5-overexpressing cell lines,3T3 and Raji. The cells were then washed, and the staining was performedusing the following steps: the cells can be first stained with purifiedscFv phage clones, and followed by staining with a mouse anti-M13 mAb,and finally the horse anti-mouse Ig's conjugate to PE. Each step of thestaining was completed between 30-60 minutes on ice and the cells werewashed twice between each step of the staining.

76 unique clones that were specific for FcRL5 were identifed andconfirmed by screening (see Tables 1-229 and FIG. 2).

Example 3—Selection of ScFv Specific for Domain 9 of FcRL5

FcRL5 contains 9 extracellular immunoglobulin-like domains (domains 1-9)and can be present within a cell in a soluble isoform, aglycosyl-phosphotidyl inositol (GPI)-anchor type isoform and atransmembrane-type isoform (FIG. 3A). As shown in FIG. 2A, thetransmembrane-type isoform of FcRL5 has domain 9; whereas, the solubleisoform and the GPI-anchor type isoform do not.

To test if the scFvs were specific to domain 9 of FcRL5, the 76 cloneswere further screened on 3T3 cells overexpressing an vector encodingFcRL5 with a domain 9 deletion (FcRL5Δdom9) and further screened on Rajicells overexpressing full-length FcRL5 (FIG. 4B-D). Some clones showedeither reduced or diminished binding towards FcRL5-domain 9deletion-overexpressing 3T3 cells compared to binding towardsFcRL5-overexpressing 3T3 cells. FIGS. 4, 5, 6, 7 and 8 shows thespecificity of ET200-39, ET200-104, ET200-105, ET200-109 and ET200-117for domain 9 of FcRL5, respectively.

Example 4—Construct of Murine FcRL5-Specific CARs

For generation of a scFv targeting human FcRL5, two commerciallyavailable mouse hybridomas binding different extracellular epitopes onhuman FcRL5 (Franco (2013); Ise et al. (2005); Ise et al. (2006)) wereobtained. From these hybridomas, two scFvs targeting human FcRL5 wereobtained. One scFv was generated by synthesizing the heavy and lightchain variable region of murine anti-human FcRL5 antibody F56 asdescribed in Ise et al. (2005) with a G4S linker having the amino acidsequence of SEQ ID NO:897. A second scFv was generated by synthesizingthe heavy and light chain variable region of murine anti-human FcRL5antibody F119 as described in Ise et al. (2005) with a G45 linker havingthe amino acid sequence of SEQ ID NO:897.

Two FcRL5 CARs were generated: F56 FcRL5-28z CAR and F119 FcRL5-28z CAR.F56 FcRL5-28z CAR and F119 FcRL5-28z CAR have similar structure, e.g.,each has a transmembrance domain comprising a CD28 polypeptide, and anintracellular domain comprising a CD3ζ polypeptide and a co-stimulatorysignaling region that comprises a CD28 polypeptide, as shown in FIG. 9A.F56 FcRL5-28z CAR comprises an scFv derived from antibody F56, and F119FcRL5-28z CAR comprises an scFv derived from antibody F119. Each of F56FcRL5-28z CAR and F119 FcRL5-28z CAR were cloned into a retroviralvector 293galv9. Human T cells (unselected (CD4 and CD8) human T cellsfrom a healthy donor) were transduced with each of F56 FcRL5-28z CAR andF119 FcRL5-28z CAR such that the T cells expressed F56 FcRL5-28z CAR orF119 FcRL5-28z CAR.

Example 5—Construct of Human FcRL5-Specific CARs

This Example discloses the generation of CARs targeting human FcRL5using the fully human scFvs described herein. ET200-31 scFv, ET200-39scFv, ET200-69 scFv, ET200-104 scFv, ET200-105 scFv, ET200-109 scFv andET200-117 scFvs were used to generate second generation FcRL5-targetedCARs designated as 31 FcRL5 BBz CAR, 39 FcRL5 BBz CAR, 69 FcRL5 BBz CAR,104 FcRL5 BBz CAR, 105 FcRL5 BBz CAR, 109 FcRL5 BBz CAR and 117 FcRL5BBz CAR with either a 4-1BB co-stimulatory domain and a CD3ζ polypeptide(see FIGS. 9B-16). The FcRL5-targeted 4-1BB containing CARs have asimilar structure, e.g., each has a CD8a polypeptide transmembranedomain, and an intracellular domain comprising co-stimulatory signalingregion consisting of a CD3ζ polypeptide and a 4-1BB polypeptide, asshown in FIG. 9B. Each of these FcRL5-targeted CARs were cloned into anSFG retroviral vector, as an example the 4-1BB containing CAR vectorsare shown in FIGS. 10-16. These viral vectors are then transduced intoHEK 293galv9 viral packaging cells in order to generate a stablepackaging line for generation of CAR+ T cells.

Example 6—Expression of Human FcRL5-Specific CARs in T Cells

Human primary T cells were transduced using supernatant from retroviralgalv9 HEK 293 packaging cells to express a FcRL5-targeted 4-1BBz CAR(generated using the anti-FcRL5 ET200-104 scFv). The cell surfaceexpression of the FcRL5-targeted CAR was determined by binding torecombinant human FcRL5 which was modified to contain a His tag followedby the binding of a PE conjugated anti-HIS tag secondary antibody, asshown in FIG. 17. Cell surface detection was validated by flowcytometry. As shown in FIG. 17, the FcRL5-targeted CAR was expressed onthe transduced T cells.

Example 7—Cytotoxicity of Human FcRL5-Specific CARs

The cytotoxic effects of the FcRL5-targeted 4-1BB CAR T cells wereanalyzed using Raji (a Burkett's lymphoma cell line) cells transduced toexpress luciferase and FcRL5 antigen or the control GPRCSD (anirrelevant antigen). T cells expressing the 4-1BB CAR generated usingthe anti-FcRL5 ET200-69 scFv were used in these experiments (referred toherein as “αFcRL5-69 BBz”). The number of live cells is determined after36 h co-culture by bioluminescent imaging (BLI). As shown in FIG. 18,FcRL5-targeted CAR T cells specifically lysed Raji cells transduced toexpress luciferase and FcRL5 antigen (FIG. 18A) but not control GPRCSDexpressing Raji cells which are lysed by GPRCSD-targeted CAR T cells(FIG. 18B).

Example 8—Cytokine Secretion of Human FcRL5-Specific CARs

This Example describes the cytokine secretion of FcRL5-targeted CAR Tcells. T cells expressing the 4-1BB CAR generated using the anti-FcRL5ET200-69 scFv were used in these experiments. IL-2, INFγ, and TNFαsecretion after 24 h co-culture of FcRL5 targeted CAR T cells on amonolayer of 3T3 cells transduced with either FcRL5 or CD19 was assessedby Luminex multiplex analysis. As shown in FIG. 19, signaling throughthe CAR of FcRL5-targeted CAR T cells induced cytokine secretionconsistent with T cell activation.

Example 9—Proliferation of Human FcRL5-Specific CARs

This Example describes the proliferation of FcRL5-targeted CAR T cellsupon antigen stimulation. T cells expressing the 4-1BB CAR generatedusing the anti-FcRL5 ET200-69 scFv was used in these experiments.500,000 FcRL5- or CD19-targeted CAR+ T cells/ml were placed on amonolayer of 3T3 cells that have been transduced with either FcRL5 orCD19 (3T3-FcRL; 3T3-CD19). After 4 days, CAR+ T cells were stained andcounted by flow cytometry with the inclusion of a known concentration ofcounting microbeads. As shown in FIG. 20, antigen stimulation ofFcRL5-targeted CAR T cells induced proliferation. FcRL5-targeted CAR Tcells co-cultured with 3T3-FcRL5 cells expanded to be 2.9 times greaterthen FcRL5-targeted CAR T cells co-cultured with 3T3-CD19 cells, whilecontrol CD19 targeted CAR T cells co-cultured with 3T3-CD19 cellssimilarly expanded to be 2.5 fold greater then CD19 targeted CAR T cellsco-cultured with 3T3-FcRL5 cells (FIG. 20).

Example 10—Epitope Mapping of Human Anti-FcRL5 Antibodies

Two anti-FcRL5 bispecific antibodies, ET200-104 and ET200-117, wereanalyzed by Pepscan to determine epitope specificity. See Table 239. Thetarget protein is human FcRL5 comprising amino acids 1-851 of SEQ ID NO:899.

TABLE 239 Name Origin Concentration Location ET200-104 human 2.0 mg/ml+4° C./22 bispecific scFV ET200-117 human 1.6 mg/ml +4° C./22 bispecificscFV

Methods

The principles of clips technology. CLIPS technology structurally fixespeptides into defined three-dimensional structures. This results infunctional mimics of even the most complex binding sites. CLIPStechnology is now routinely used to shape peptide libraries into single,double or triple looped structures as well as sheet- and helix-likefolds (FIG. 21).

Combinatorial clips library screening in detail. CLIPS library screeningstarts with the conversion of the target protein into a library of up to10,000 overlapping peptide constructs, using a combinatorial matrixdesign. On a solid carrier, a matrix of linear peptides is synthesized,which are subsequently shaped into spatially defined CLIPS constructs(FIG. 22). Constructs representing both parts of the discontinuousepitope in the correct conformation bind the antibody with highaffinity, which is detected and quantified. Constructs presenting theincomplete epitope bind the antibody with lower affinity, whereasconstructs not containing the epitope do not bind at all. Affinityinformation is used in iterative screens to define the sequence andconformation of epitopes in detail.

Heat map analysis. A heat map is a graphical representation of datawhere the values taken by a variable in a two-dimensional map arerepresented as colors. For double-looped CLIPS peptides, such atwo-dimensional map can be derived from the independent sequences of thefirst and second loops. For example, the sequences of the 16 CLIPSpeptides depicted in FIG. 24 are effectively permutations of 4 uniquesub-sequences in loop 1 (colored in blue in FIG. 23) and 4 uniquesub-sequences in loop 2 (colored in green in FIG. 23). Thus, theobserved ELISA data (colored in red in FIG. 24A) can be plotted in a 4×4matrix, where each X coordinate corresponds to the sequence of the firstloop, and each Y coordinate corresponds to the sequence of the secondloop. For instance, the ELISA value observed for CLIPS peptideCLSSERERVEDLFEYECELLTSEPIFHCRQEDC (indicated with an arrow in FIG. 23A)can be found at the third row, third column of FIG. 24B (indicated withan arrow and a red square). To further facilitate the visualization,ELISA values can be replaced with colors from a continuous gradient. Inthis case, extremely low values are colored in green, extremely highvalues are colored in red, and average values are colored in black (seeFIG. 24C). For the aforementioned example, the average value is 0.71.When this color map is applied to the data matrix depicted in FIG. 24B,a color heat map is obtained (see FIG. 24D, the original data is stillindicated for extra clarity).

Synthesis of peptides. To reconstruct epitopes of the target molecule alibrary of peptides was synthesized. An amino functionalizedpolypropylene support was obtained by grafting with a proprietaryhydrophilic polymer formulation, followed by reaction witht-butyloxycarbonyl-hexamethylenediamine (BocHMDA) usingdicyclohexylcarbodiimide (DCC) with Nhydroxybenzotriazole (HOBt) andsubsequent cleavage of the Boc-groups using trifluoroacetic acid (TFA).Standard Fmoc-peptide synthesis was used to synthesize peptides on theamino-functionalized solid support by custom modified JANUS liquidhandling stations (Perkin Elmer). Synthesis of structural mimics wasdone using Pepscan's proprietary Chemically Linked Peptides on Scaffolds(CLIPS) technology. CLIPS technology allows to structure peptides intosingle loops, doubleloops, triple loops, sheet-like folds, helix-likefolds and combinations thereof. CLIPS templates are coupled to cysteineresidues. The side-chains of multiple cysteines in the peptides werecoupled to one or two CLIPS templates. For example, a 0.5 mM solution ofthe P2 CLIPS (2,6-bis(bromomethyl)pyridine) was dissolved in ammoniumbicarbonate (20 mM, pH 7.8)/acetonitrile (1:3(v/v)). This solution wasadded onto the peptide arrays. The CLIPS template bound to side-chainsof two cysteines as present in the solid-phase bound peptides of thepeptide-arrays (455 wells plate with 3 μl wells). The peptide arrayswere gently shaken in the solution for 30 to 60 minutes while completelycovered in solution. Finally, the peptide arrays were washed extensivelywith excess of H₂O and sonicated in disrupt-buffer containing 1%SDS/0.1% beta-mercaptoethanol in PBS (pH 7.2) at 70° C. for 30 minutes,followed by sonication in H₂O for another 45 minutes. The T3 CLIPScarrying peptides were made in a similar way but now with threecysteines.

ELISA Screening. The binding of antibody to each of the synthesizedpeptides was tested in a PEPSCAN-based ELISA. The peptide arrays wereincubated with primary antibody solution (overnight at 4° C.). Afterwashing, the peptide arrays were incubated with a 1/1000 dilution of anappropriate antibody peroxidase conjugate (SBA) for one hour at 25° C.After washing, the peroxidase substrate2,2′-azino-di-3-ethylbenzthiazoline sulfonate (ABTS) and 2 μl/ml of 3percent H₂O₂ were added. After one hour, the color development wasmeasured. The color development was quantified with a charge coupleddevice (CCD)—camera and an image processing system.

Data processing. The values obtained from the CCD camera ranged from 0to 3000 mAU, similar to a standard 96-well plate ELISA-reader. Theresults were quantified and stored into the Peplab database.Occasionally a well contained an air-bubble resulting in afalse-positive value, the cards were manually inspected and any valuescaused by an air-bubble were scored as 0.

Synthesis quality control. To verify the quality of the synthesizedpeptides, a separate set of positive and negative control peptides wassynthesized in parallel. These were screened with antibody 57.9 (ref.Posthumus et al., J. Virology, 1990, 64:3304-3309).

Results

Screening. Antibody binding depends on a combination of factors,including concentration of the antibody and the amounts and nature ofcompeting proteins in the ELISA buffer. Also, the pre-coat conditions(the specific treatment of the peptide arrays prior to incubation withthe experimental sample) affected binding. These details are summed upin Table 240. For the Pepscan Buffer and Preconditioning (SQ), thenumbers indicate the relative amount of competing protein (a combinationof horse serum and ovalbumin).

TABLE 240 Screening conditions Label Dilution Sample BufferPre-conditioning ET200-104 8 μg/ml PBS-Tween PBS-Tween ET200-117 3 μg/mlPBS-Tween 0.1% SQ

Antibodies ET200-104 and ET200-117 were coated at 1 μg/ml on a NuncMaxisorp plate for ELISA and detected with Goat Anti-Human Ig-HRP(Southern Biotech; #2010/05), the same conjugate that is used inminicard screenings. For ET200-104 and ET200-117 signal >1 OD wasobtained for some dilutions of the secondary Ab, indicating that thesecondary antibody is well suited for detection of these mAbs.

Herceptin was used as an internal negative control at high concentrationin the absence of blocking buffer. Herceptin bound peptides with commonsequences LRGSPLILYRF, LRGSSPILYWF and APRGSPPILYW (FIG. 25). Peptidescontaining aforementioned sequences were excluded from epitopecandidates for test samples.

When tested under low stringency conditions and at a high concentrationantibody ET200-104 binds multiple peptide motifs in all sets (FIG. 26).The majority of peptides bound were suspected to be the result ofnon-specific hydrophic interactions based on the results obtained forHerceptin (internal negative control). However, binding of peptidescontaining motif ₆₅₇SRPILTFRAPR₆₆₇ was proposed to be specific, and wasuniquely attributed to sample ET200-104.

When tested under low stringency conditions antibody ET200-117 resultedin weak binding of multiple peptide motifs on all sets. Cumulative dataanalysis of data obtained for all sets suggests that the antibodyuniquely recognizes a region containing peptide stretch₈₂₉RSETVTLYITGL₈₄₀ in domain 9 of Fc receptor-like protein 5 distinctfrom the Herceptin internal negative control and ET200-104. Again themajority of other peptides bound were suspected to be the result ofunspecific hydrophic interactions that shared as the same bindingpattern was recorded under low stringency conditions for antibodyET200-104.

CONCLUSIONS

Cumulative data analysis of results collected for ET200-104, andET200-117 vs. Herceptin suggest that antibody ET200-104 targets residues₆₅₇SRPILTFRAPR₆₆₇ within domain 8 of Fc receptor-like protein 5 andantibody ET200-117 targets residues ₈₂₉RSETVTLYITGL₈₄₀ within domain 9.Additionally, for both samples multiple signals were recorded withpeptides non-specifically bound by Herceptin. The epitope candidateidentified for ET200-104 was visualized using a publically available 3Dmodel of Fc receptor-like protein 5 (FIG. 27). The epitope candidate forET200-117 lies within the non-modeled part of the target and thereforecannot be visualized.

REFERENCES

-   1. Franco, A., et al. Human Fc receptor-like 5 binds intact IgG via    mechanisms distinct from those of Fc receptors. Journal of    immunology 190, 5739-5746 (2013).-   2. Dement-Brown, J., et al. Fc receptor-like 5 promotes B cell    proliferation and drives the development of cells displaying    switched isotypes. Journal of leukocyte biology 91, 59-67 (2012).-   3. Ise, T., et al. Elevation of soluble CD307 (IRTA2/FcRH5) protein    in the blood and expression on malignant cells of patients with    multiple myeloma, chronic lymphocytic leukemia, and mantle cell    lymphoma. Leukemia 21, 169-174 (2007).-   4. Elkins, K., et al. FcRL5 as a target of antibody-drug conjugates    for the treatment of multiple myeloma. Molecular cancer therapeutics    11, 2222-2232 (2012).-   5. Hatzivassiliou, G., et al. IRTA1 and IRTA2, novel immunoglobulin    superfamily receptors expressed in B cells and involved in    chromosome 1q21 abnormalities in B cell malignancy. Immunity 14,    277-289 (2001).-   6. An, G., et al. Chromosome 1q21 gains confer inferior outcomes in    multiple myeloma treated with bortezomib but copy number variation    and percentage of plasma cells involved have no additional    prognostic value. Haematologica 99, 353-359 (2014).-   7. Ise, T., et al. Immunoglobulin superfamily receptor translocation    associated 2 protein on lymphoma cell lines and hairy cell leukemia    cells detected by novel monoclonal antibodies. Clinical cancer    research: an official journal of the American Association for Cancer    Research 11, 87-96 (2005).-   8. Ise, T., Kreitman, R. J., Pastan, I. & Nagata, S. Sandwich ELISAs    for soluble immunoglobulin superfamily receptor    translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human    sera. Clinical chemistry and laboratory medicine: CCLM/FESCC 44,    594-602 (2006).-   9. Brentjens, R. J., et al. Safety and persistence of adoptively    transferred autologous CD19-targeted T cells in patients with    relapsed or chemotherapy refractory B-cell leukemias. Blood 118,    4817-4828 (2011).-   10. Brentjens, R. J., et al. Eradication of systemic B-cell tumors    by genetically targeted human T lymphocytes co-stimulated by CD80    and interleukin-15. Nature medicine 9, 279-286 (2003).-   11. Brentjens, R. J., et al. CD19-Targeted T Cells Rapidly Induce    Molecular Remissions in Adults with Chemotherapy-Refractory Acute    Lymphoblastic Leukemia. Science translational medicine 5, 177ra138    (2013).-   12. Davila, M. L., et al. Efficacy and Toxicity Management of 19-28z    CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Science    translational medicine 6, 224ra225 (2014).-   13. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2013.    CA: a cancer journal for clinicians 63, 11-30 (2013).-   14. Boyd, K. D., et al. The clinical impact and molecular biology of    del(17p) in multiple myeloma treated with conventional or    thalidomide-based therapy. Genes, chromosomes & cancer 50, 765-774    (2011).-   15. Shaughnessy, J. D., Jr., et al. A validated gene expression    model of high-risk multiple myeloma is defined by deregulated    expression of genes mapping to chromosome 1. Blood 109, 2276-2284    (2007).-   16. Gahrton, G., et al. Allogeneic bone marrow transplantation in    multiple myeloma. European Group for Bone Marrow Transplantation.    The New England journal of medicine 325, 1267-1273 (1991).-   17. Pegram, H. J., et al. Tumor-targeted T cells modified to secrete    IL-12 eradicate systemic tumors without need for prior conditioning.    Blood 119, 4133-4141 (2012).-   18. Sabrina Bertilaccio, M. T., et al. Low-Dose Lenalidomide    Improves CAR-Based Immunotherapy In CLL By Reverting T-Cell Defects    In Vivo. Blood 122, 4171 (2013).-   19. Bataille, R., et al. The phenotype of normal, reactive and    malignant plasma cells. Identification of “many and multiple    myelomas” and of new targets for myeloma therapy. Haematologica 91,    1234-1240 (2006).-   20. Morgan, R. A., et al. Case report of a serious adverse event    following the administration of T cells transduced with a chimeric    antigen receptor recognizing ERBB2. Molecular therapy: the journal    of the American Society of Gene Therapy 18, 843-851 (2010).-   21. Brentjens, R. J., et al. Safety and persistence of adoptively    transferred autologous CD19-targeted T cells in patients with    relapsed or chemotherapy refractory B-cell leukemias. Blood 118,    4817-4828 (2011).-   22. Brentjens, R. J., et al. CD19-targeted T cells rapidly induce    molecular remissions in adults with chemotherapy-refractory acute    lymphoblastic leukemia. Science translational medicine 5, 177ra138    (2013).-   23. Hunder, N. N., et al. Treatment of metastatic melanoma with    autologous CD4+ T cells against NY-ESO-1. N. Engl. J. Med. 358,    2698-2703 (2008).-   24. Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A. &    Dudley, M. E. Adoptive cell transfer: a clinical path to effective    cancer immunotherapy. Nat.Rev.Cancer 8, 299-308 (2008).-   25. Dudley, M. E., et al. Adoptive cell therapy for patients with    metastatic melanoma: evaluation of intensive myeloablative    chemoradiation preparative regimens. J Clin Oncol 26, 5233-5239    (2008).-   26. Brentjens, R. J., et al. Genetically targeted T cells eradicate    systemic acute lymphoblastic leukemia xenografts. Clin. Cancer Res.    13, 5426-5435 (2007).-   27. Gade, T. P., et al. Targeted elimination of prostate cancer by    genetically directed human T lymphocytes. Cancer Res. 65, 9080-9088    (2005).-   28. Maher, J., Brentjens, R. J., Gunset, G., Riviere, I. &    Sadelain, M. Human T-lymphocyte cytotoxicity and proliferation    directed by a single chimeric TCRzeta/CD28 receptor. Nat.    Biotechnol. 20, 70-75 (2002).-   29. Kershaw, M. H., et al. Gene-engineered T cells as a superior    adjuvant therapy for metastatic cancer. J Immunol 173, 2143-2150    (2004).-   30. Sadelain, M., Brentjens, R. & Riviere, I. The promise and    potential pitfalls of chimeric antigen receptors. Curr Opin Immunol    (2009).-   31. Hollyman, D., et al. Manufacturing validation of biologically    functional T cells targeted to CD19 antigen for autologous adoptive    cell therapy. J Immunother 32, 169-180 (2009).-   32. Sadelain, M., Brentjens, R. & Riviere, I. The basic principles    of chimeric antigen receptor design. Cancer discovery 3, 388-398    (2013).-   33. Riviere, I., Sadelain, M. & Brentjens, R. J. Novel strategies    for cancer therapy: the potential of genetically modified T    lymphocytes. Curr Hematol Rep 3, 290-297 (2004).-   34. Stephan, M. T., et al. T cell-encoded CD80 and 4-1BBL induce    auto- and transco-stimulation, resulting in potent tumor rejection.    Nat. Med. 13, 1440-1449 (2007).-   35. Krause, A., et al. Antigen-dependent CD28 signaling selectively    enhances survival and proliferation in genetically modified    activated human primary T lymphocytes. J Exp Med 188, 619-626    (1998).-   36. Gong, M. C., et al. Cancer patient T cells genetically targeted    to prostate-specific membrane antigen specifically lyse prostate    cancer cells and release cytokines in response to prostate-specific    membrane antigen. Neoplasia. 1, 123-127 (1999).-   37. Lyddane, C., et al. Cutting Edge: CD28 controls dominant    regulatory T cell activity during active immunization. J. Immunol.    176, 3306-3310 (2006).

From the foregoing description, it will be apparent that variations andmodifications may be made to the invention described herein to adopt itto various usages and conditions. Such embodiments are also within thescope of the following claims.

All patents and publications and sequences referred to by accession orreference number mentioned in this specification are herein incorporatedby reference to the same extent as if each independent patent andpublication and sequence was specifically and individually indicated tobe incorporated by reference.

What is claimed is:
 1. A chimeric antigen receptor (CAR), comprising anextracellular antigen-binding domain, a transmembrane domain and anintracellular domain, wherein the extracellular antigen-binding domainthat specifically binds to Fc Receptor-like 5 (FcRL5).
 2. The CAR ofclaim 1, wherein the extracellular antigen-binding domain is asingle-chain variable fragment (scFv).
 3. The CAR of claim 2, whereinthe extracellular antigen-binding domain is a murine scFv.
 4. The CAR ofclaim 2, wherein the extracellular antigen-binding domain is a humanscFv.
 5. The CAR of claim 1, wherein the extracellular antigen-bindingdomain is a Fab, which is optionally crosslinked.
 6. The CAR of claim 1,wherein the extracellular antigen-binding domain is a F(ab′)₂.
 7. TheCAR of any one of claims 2-6, one or more of the scFv, Fab and F(ab′)₂are comprised in a fusion protein with a heterologous sequence to formthe extracellular antigen-binding domain.
 8. The CAR of any one ofclaims 1-7, wherein the extracellular antigen-binding domain of the CARbinds to FcRL5 with a binding affinity (K_(d)) of from about 1×10⁻⁹M toabout 3×10⁻⁶M.
 9. The CAR of any one of claims 1-8, wherein theextracellular antigen-binding domain of the CAR binds to domain 7,domain 8 or domain 9 of FcRL5 with a binding affinity (K_(d)) of fromabout 1×10⁻⁹M to about 3×10⁻⁶M.
 10. The CAR of any one of claims 1-9,wherein the extracellular antigen-binding domain comprises a light chainvariable region comprising an amino acid sequence that is at least 80%,81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98% or 99% homologous to an amino acid sequence selectedfrom the group consisting of SEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:11, SEQID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQ ID NO:27, SEQ ID NO:31, SEQ IDNO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ ID NO:47, SEQ ID NO:51, SEQ IDNO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:67, SEQ ID NO:71, SEQ IDNO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ ID NO:87, SEQ ID NO:91, SEQ IDNO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ IDNO:115, SEQ ID NO:119, SEQ ID NO:123, SEQ ID NO:127, SEQ ID NO:131, SEQID NO:135, SEQ ID NO:139, SEQ ID NO:143, SEQ ID NO:147, SEQ ID NO:151,SEQ ID NO:155, SEQ ID NO:159, SEQ ID NO:163, SEQ ID NO:167, SEQ IDNO:171, SEQ ID NO:175, SEQ ID NO:179, SEQ ID NO:183, SEQ ID NO:187, SEQID NO:191, SEQ ID NO:195, SEQ ID NO:199, SEQ ID NO:203, SEQ ID NO:207,SEQ ID NO:211, SEQ ID NO:215, SEQ ID NO:219, SEQ ID NO:223, SEQ IDNO:227, SEQ ID NO:231, SEQ ID NO:235, SEQ ID NO:239, SEQ ID NO:243, SEQID NO:247, SEQ ID NO:251, SEQ ID NO:255, SEQ ID NO:259, SEQ ID NO:263,SEQ ID NO:267, SEQ ID NO:271, SEQ ID NO:275, SEQ ID NO:279, SEQ IDNO:283, SEQ ID NO:287, SEQ ID NO:291, SEQ ID NO:295, SEQ ID NO:299, SEQID NO:303, SEQ ID NO:917 and SEQ ID NO:921, wherein the extracellularantigen-binding domain binds to FcRL5.
 11. The CAR of any one of claims1-9, wherein the extracellular antigen-binding domain comprises a heavychain variable region comprising an amino acid sequence that is at least80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%,94%, 95%, 96%, 97%, 98% or 99% homologous to an amino acid sequenceselected from the group consisting of SEQ ID NO:4, SEQ ID NO:8, SEQ IDNO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQ ID NO:28, SEQ IDNO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ ID NO:48, SEQ IDNO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:68, SEQ IDNO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ IDNO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:108, SEQ IDNO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQ ID NO:128, SEQID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144, SEQ ID NO:148,SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:164, SEQ IDNO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQ ID NO:184, SEQID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200, SEQ ID NO:204,SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ ID NO:220, SEQ IDNO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQ ID NO:240, SEQID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256, SEQ ID NO:260,SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ ID NO:276, SEQ IDNO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQ ID NO:296, SEQID NO:300, SEQ ID NO:304, SEQ ID NO:915 and SEQ ID NO:919, wherein theextracellular antigen-binding domain binds to FcRL5.
 12. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises (a) a light chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:3,SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQ ID NO:23, SEQID NO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ ID NO:43, SEQ IDNO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ ID NO:63, SEQ IDNO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ ID NO:83, SEQ IDNO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ ID NO:103, SEQ IDNO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQ ID NO:123, SEQID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139, SEQ ID NO:143,SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ ID NO:159, SEQ IDNO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQ ID NO:179, SEQID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195, SEQ ID NO:199,SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ ID NO:215, SEQ IDNO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQ ID NO:235, SEQID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251, SEQ ID NO:255,SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ ID NO:271, SEQ IDNO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQ ID NO:291, SEQID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917 and SEQ IDNO:921; and (b) a heavy chain variable region comprising an amino acidsequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%,89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% homologous to anamino acid sequence selected from the group consisting of SEQ ID NO:4,SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQID NO:28, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ IDNO:48, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ IDNO:68, SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ IDNO:88, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ IDNO:108, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQID NO:128, SEQ ID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144,SEQ ID NO:148, SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ IDNO:164, SEQ ID NO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQID NO:184, SEQ ID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200,SEQ ID NO:204, SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ IDNO:220, SEQ ID NO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQID NO:240, SEQ ID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256,SEQ ID NO:260, SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ IDNO:276, SEQ ID NO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQID NO:296, SEQ ID NO:300, SEQ ID NO:304, SEQ ID NO:915 and SEQ IDNO:919, wherein the extracellular antigen-binding domain binds to FcRL5.13. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQID NO:23, SEQ ID NO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ IDNO:43, SEQ ID NO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ IDNO:63, SEQ ID NO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ IDNO:83, SEQ ID NO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ IDNO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQID NO:123, SEQ ID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139,SEQ ID NO:143, SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ IDNO:159, SEQ ID NO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQID NO:179, SEQ ID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195,SEQ ID NO:199, SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ IDNO:215, SEQ ID NO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQID NO:235, SEQ ID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251,SEQ ID NO:255, SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ IDNO:271, SEQ ID NO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQID NO:291, SEQ ID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917,SEQ ID NO:921 and conservative modifications thereof.
 14. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises a heavy chain variable region comprising an amino acidsequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:8,SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQ ID NO:28,SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ ID NO:48,SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:68,SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88,SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:108,SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQ IDNO:128, SEQ ID NO:132, SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144, SEQID NO:148, SEQ ID NO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:164,SEQ ID NO:168, SEQ ID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQ IDNO:184, SEQ ID NO:188, SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200, SEQID NO:204, SEQ ID NO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ ID NO:220,SEQ ID NO:224, SEQ ID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQ IDNO:240, SEQ ID NO:244, SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256, SEQID NO:260, SEQ ID NO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ ID NO:276,SEQ ID NO:280, SEQ ID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQ IDNO:296, SEQ ID NO:300, SEQ ID NO:304, SEQ ID NO:915, SEQ ID NO:919 andconservative modifications thereof.
 15. The CAR of any one of claims1-9, wherein the extracellular antigen-binding domain comprises a heavychain variable region comprising amino acids having the sequence setforth in SEQ ID NO:915.
 16. The CAR of any one of claims 1-9, whereinthe extracellular antigen-binding domain comprises a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:917.
 17. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises a heavy chain variableregion comprising amino acids having the sequence set forth in SEQ IDNO:919.
 18. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:921.19. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:144.20. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:143.21. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:216.22. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:215.23. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:220.24. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:219.25. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:236.26. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:235.27. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:268.28. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:267.29. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:116.30. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:115.31. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a heavy chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:172.32. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises a light chain variable regioncomprising amino acids having the sequence set forth in SEQ ID NO:171.33. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises (a) a light chain variable regioncomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:3, SEQ ID NO:7, SEQ ID NO:11, SEQ ID NO:15, SEQ ID NO:19, SEQID NO:23, SEQ ID NO:27, SEQ ID NO:31, SEQ ID NO:35, SEQ ID NO:39, SEQ IDNO:43, SEQ ID NO:47, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:59, SEQ IDNO:63, SEQ ID NO:67, SEQ ID NO:71, SEQ ID NO:75, SEQ ID NO:79, SEQ IDNO:83, SEQ ID NO:87, SEQ ID NO:91, SEQ ID NO:95, SEQ ID NO:99, SEQ IDNO:103, SEQ ID NO:107, SEQ ID NO:111, SEQ ID NO:115, SEQ ID NO:119, SEQID NO:123, SEQ ID NO:127, SEQ ID NO:131, SEQ ID NO:135, SEQ ID NO:139,SEQ ID NO:143, SEQ ID NO:147, SEQ ID NO:151, SEQ ID NO:155, SEQ IDNO:159, SEQ ID NO:163, SEQ ID NO:167, SEQ ID NO:171, SEQ ID NO:175, SEQID NO:179, SEQ ID NO:183, SEQ ID NO:187, SEQ ID NO:191, SEQ ID NO:195,SEQ ID NO:199, SEQ ID NO:203, SEQ ID NO:207, SEQ ID NO:211, SEQ IDNO:215, SEQ ID NO:219, SEQ ID NO:223, SEQ ID NO:227, SEQ ID NO:231, SEQID NO:235, SEQ ID NO:239, SEQ ID NO:243, SEQ ID NO:247, SEQ ID NO:251,SEQ ID NO:255, SEQ ID NO:259, SEQ ID NO:263, SEQ ID NO:267, SEQ IDNO:271, SEQ ID NO:275, SEQ ID NO:279, SEQ ID NO:283, SEQ ID NO:287, SEQID NO:291, SEQ ID NO:295, SEQ ID NO:299, SEQ ID NO:303, SEQ ID NO:917,SEQ ID NO:921 and conservative modifications thereof; and (b) a heavychain variable region comprising an amino acid sequence selected fromthe group consisting of SEQ ID NO:4, SEQ ID NO:8, SEQ ID NO:12, SEQ IDNO:16, SEQ ID NO:20, SEQ ID NO:24, SEQ ID NO:28, SEQ ID NO:32, SEQ IDNO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ ID NO:48, SEQ ID NO:52, SEQ IDNO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:68, SEQ ID NO:72, SEQ IDNO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:92, SEQ IDNO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQ ID NO:128, SEQ ID NO:132,SEQ ID NO:136, SEQ ID NO:140, SEQ ID NO:144, SEQ ID NO:148, SEQ IDNO:152, SEQ ID NO:156, SEQ ID NO:160, SEQ ID NO:164, SEQ ID NO:168, SEQID NO:172, SEQ ID NO:176, SEQ ID NO:180, SEQ ID NO:184, SEQ ID NO:188,SEQ ID NO:192, SEQ ID NO:196, SEQ ID NO:200, SEQ ID NO:204, SEQ IDNO:208, SEQ ID NO:212, SEQ ID NO:216, SEQ ID NO:220, SEQ ID NO:224, SEQID NO:228, SEQ ID NO:232, SEQ ID NO:236, SEQ ID NO:240, SEQ ID NO:244,SEQ ID NO:248, SEQ ID NO:252, SEQ ID NO:256, SEQ ID NO:260, SEQ IDNO:264, SEQ ID NO:268, SEQ ID NO:272, SEQ ID NO:276, SEQ ID NO:280, SEQID NO:284, SEQ ID NO:288, SEQ ID NO:292, SEQ ID NO:296, SEQ ID NO:300,SEQ ID NO:304, SEQ ID NO:915, SEQ ID NO:919 and conservativemodifications thereof.
 34. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:915; and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:917.
 35. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:919; and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:921.
 36. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:144, and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:143.
 37. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:216, and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:215.
 38. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:220, and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:219.
 39. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:236, and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:235.
 40. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:268, and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:267.
 41. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises (a) a heavy chain variable region comprising amino acidshaving the sequence set forth in SEQ ID NO:116, and (b) a light chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:115.
 42. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises (a) a heavy chainvariable region comprising amino acids having the sequence set forth inSEQ ID NO:172, and (b) a light chain variable region comprising aminoacids having the sequence set forth in SEQ ID NO:171.
 43. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises (a) a heavy chain variable region CDR3 comprising an aminoacid sequence selected from the group consisting of SEQ ID NOs: 311,317, 323, 328, 334, 337, 342, 347, 351, 356, 362, 368, 374, 376, 380,384, 389, 394, 396, 400, 405, 408, 412, 415, 422, 427, 432, 437, 442,446, 451, 453, 456, 458, 459, 463, 464, 467, 473, 476, 482, 486, 489,492, 494, 497, 502, 507, 512, 517, 522, 527, 529, 532, 536, 539, 543,546, 550, 553, 555, 561, 567, 570, 574, 577, 578, 579, 584, 578, 587,591, 925 and 931; and (b) a light chain variable region CDR3 comprisingan amino acid sequence selected from the group consisting of SEQ ID NOs:314, 320, 325, 331, 339, 345, 350, 353, 359, 365, 371, 377, 383, 386,392, 395, 399, 402, 407, 410, 414, 418, 419, 424, 430, 435, 439, 443,449, 452, 455, 457, 462, 465, 470, 479, 485, 488, 491, 493, 495, 499,505, 509, 514, 519, 524, 528, 530, 531, 535, 541, 542, 545, 549, 554,558, 564, 569, 573, 576, 581, 592, 928 and
 934. 44. The CAR of any oneof claims 1-9, wherein the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising an aminoacid sequence selected from the group consisting of SEQ ID NOs: 309,315, 321, 326, 332, 335, 340, 346, 354, 360, 366, 372, 378, 387, 393,403, 411, 420, 425, 436, 440, 444, 471, 480, 500, 510, 515, 520, 525,537, 551, 559, 565, 582, 589, 923 and 929; (b) a heavy chain variableregion CDR2 comprising an amino acid sequence selected from the groupconsisting of SEQ ID NOs: 310, 316, 322, 327, 333, 336, 341, 355, 361,367, 373, 379, 388, 404, 412, 421, 426, 431, 441, 445, 450, 466, 472,475, 481, 496, 501, 506, 511, 516, 521, 526, 538, 552, 560, 566, 583,590, 924 and 930; (c) a heavy chain variable region CDR3 comprising anamino acid sequence selected from the group consisting of SEQ ID NOs:311, 317, 323, 328, 334, 337, 342, 347, 351, 356, 362, 368, 374, 376,380, 384, 389, 394, 396, 400, 405, 408, 412, 415, 422, 427, 432, 437,442, 446, 451, 453, 456, 458, 459, 463, 464, 467, 473, 476, 482, 486,489, 492, 494, 497, 502, 507, 512, 517, 522, 527, 529, 532, 536, 539,543, 546, 550, 553, 555, 561, 567, 570, 574, 577, 578, 579, 584, 578,587, 591, 925 and 931; (d) a light chain variable region CDR1 comprisingan amino acid sequence selected from the group consisting of SEQ ID NOs:312, 318, 324, 329, 338, 343, 348, 352, 357, 363, 369, 381, 390, 397,401, 406, 416, 423, 428, 433, 447, 460, 468, 474, 477, 483, 490, 498,503, 508, 518, 533, 540, 544, 547, 556, 562, 568, 571, 580, 585, 588,926 and 931; (e) a light chain variable region CDR2 comprising an aminoacid sequence selected from the group consisting of SEQ ID NOs: 313,319, 330, 344, 349, 358, 364, 370, 382, 385, 391, 398, 409, 417, 429,434, 438, 448, 454, 461, 469, 478, 484, 487, 504, 513, 523, 534, 429,448, 548, 557, 563, 572, 575, 586, 927 and 933; and (f) a light chainvariable region CDR3 comprising an amino acid sequence selected from thegroup consisting of SEQ ID NOs: 314, 320, 325, 331, 339, 345, 350, 353,359, 365, 371, 377, 383, 386, 392, 395, 399, 402, 407, 410, 414, 418,419, 424, 430, 435, 439, 443, 449, 452, 455, 457, 462, 465, 470, 479,485, 488, 491, 493, 495, 499, 505, 509, 514, 519, 524, 528, 530, 531,535, 541, 542, 545, 549, 554, 558, 564, 569, 573, 576, 581, 592, 928 and934.
 45. The CAR of any one of claims 1-9, wherein the extracellularantigen-binding domain comprises (a) a heavy chain variable region CDR1comprising amino acids having the sequence set forth in SEQ ID NO:923 orconservative modifications thereof, (b) a heavy chain variable regionCDR2 comprising amino acids having the sequence set forth in SEQ IDNO:924 or conservative modifications thereof, (c) a heavy chain variableregion CDR3 comprising amino acids having the sequence set forth in SEQID NO:925 or conservative modifications thereof, (d) a light chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:926 or conservative modifications thereof, (e) alight chain variable region CDR2 comprising amino acids having thesequence set forth in SEQ ID NO:927 or conservative modificationsthereof, and (f) a light chain variable region CDR3 comprising aminoacids having the sequence set forth in SEQ ID NO:928 or conservativemodifications thereof.
 46. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises (a) a heavy chainvariable region CDR1 comprising amino acids having the sequence setforth in SEQ ID NO:929 or conservative modifications thereof, (b) aheavy chain variable region CDR2 comprising amino acids having thesequence set forth in SEQ ID NO:930 or conservative modificationsthereof, (c) a heavy chain variable region CDR3 comprising amino acidshaving the sequence set forth in SEQ ID NO:931 or conservativemodifications thereof, (d) a light chain variable region CDR1 comprisingamino acids having the sequence set forth in SEQ ID NO:932 orconservative modifications thereof, (e) a light chain variable regionCDR2 comprising amino acids having the sequence set forth in SEQ IDNO:933 or conservative modifications thereof, and (f) a light chainvariable region CDR3 comprising amino acids having the sequence setforth in SEQ ID NO:934 or conservative modifications thereof.
 47. TheCAR of any one of claims 1-9, wherein the extracellular antigen-bindingdomain comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:411 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:412 or conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:463 or conservative modifications thereof; (d) alight chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:318 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:319or conservative modifications thereof; and (f) a light chain variableregion CDR3 comprising the amino acid sequence of SEQ ID NO:419.
 48. TheCAR of any one of claims 1-9, wherein the extracellular antigen-bindingdomain comprises (a) a heavy chain variable region CDR1 comprising theamino acid sequence of SEQ ID NO:515 or conservative modificationsthereof; (b) a heavy chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:516 or conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:517 or conservative modifications thereof; (d) alight chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:318 or conservative modifications thereof; (e) a light chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:319or conservative modifications thereof; and (f) a light chain variableregion CDR3 comprising the amino acid sequence of SEQ ID NO:531 orconservative modifications thereof.
 49. The CAR of any one of claims1-9, wherein the extracellular antigen-binding domain comprises (a) aheavy chain variable region CDR1 comprising the amino acid sequence ofSEQ ID NO:403 or conservative modifications thereof; (b) a heavy chainvariable region CDR2 comprising the amino acid sequence of SEQ ID NO:404or conservative modifications thereof; (c) a heavy chain variable regionCDR3 comprising the amino acid sequence of SEQ ID NO:532 or conservativemodifications thereof; (d) a light chain variable region CDR1 comprisingthe amino acid sequence of SEQ ID NO:533 or conservative modificationsthereof; (e) a light chain variable region CDR2 comprising the aminoacid sequence of SEQ ID NO:534 or conservative modifications thereof;and (f) a light chain variable region CDR3 comprising the amino acidsequence of SEQ ID NO:535.
 50. The CAR of any one of claims 1-9, whereinthe extracellular antigen-binding domain comprises (a) a heavy chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:411or conservative modifications thereof; (b) a heavy chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:412 or conservativemodifications thereof; (c) a heavy chain variable region CDR3 comprisingthe amino acid sequence of SEQ ID NO:543 or conservative modificationsthereof; (d) a light chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:544 or conservative modifications thereof;(e) a light chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:448 or conservative modifications thereof; and (f)a light chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:545 or conservative modifications thereof.
 51. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:372 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:475 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:570 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:571or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:572 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:573 or conservativemodifications thereof.
 52. The CAR of any one of claims 1-9, wherein theextracellular antigen-binding domain comprises: (a) a heavy chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:440or conservative modifications thereof; (b) a heavy chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:441 or conservativemodifications thereof; (c) a heavy chain variable region CDR3 comprisingthe amino acid sequence of SEQ ID NO:442 or conservative modificationsthereof; (d) a light chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:329 or conservative modifications thereof;(e) a light chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:330 or conservative modifications thereof; and (f)a light chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:443 or conservative modifications thereof.
 53. The CAR of anyone of claims 1-9, wherein the extracellular antigen-binding domaincomprises: (a) a heavy chain variable region CDR1 comprising the aminoacid sequence of SEQ ID NO:309 or conservative modifications thereof;(b) a heavy chain variable region CDR2 comprising the amino acidsequence of SEQ ID NO:310 or conservative modifications thereof; (c) aheavy chain variable region CDR3 comprising the amino acid sequence ofSEQ ID NO:489 or conservative modifications thereof; (d) a light chainvariable region CDR1 comprising the amino acid sequence of SEQ ID NO:490or conservative modifications thereof; (e) a light chain variable regionCDR2 comprising the amino acid sequence of SEQ ID NO:313 or conservativemodifications thereof; and (f) a light chain variable region CDR3comprising the amino acid sequence of SEQ ID NO:491 or conservativemodifications thereof.
 54. The CAR of any one of claims 43-53, whereinone or more of the CDRs of the extracellular antigen-binding domain haveup to about 5 amino acid substitutions.
 55. The CAR of any one of claims43-53, wherein one or more of the CDRs of the extracellularantigen-binding domain have up to about 3 amino acid substitutions. 56.The CAR of any one of claims 1-55, wherein the extracellularantigen-binding domain comprises a linker between a heavy chain variableregion and a light chain variable region of the extracellularantigen-binding domain.
 57. The CAR of claim 56, wherein the linkercomprises an amino acid sequence selected from the group consisting ofSEQ ID NO:307 and SEQ ID NO:897.
 58. The CAR of any one of claims 1-57,wherein the extracellular antigen-binding domain comprises a signalpeptide that is covalently joined to the 5′ terminus of theextracellular antigen-binding domain.
 59. The CAR of any one of claims1-58, wherein the FcRL5 comprises the amino acid sequence set forth inSEQ ID NO:899.
 60. The CAR of any one of claims 1-59, wherein theextracellular antigen-binding domain binds an epitope comprising theamino acid sequence set forth in SEQ ID NO:964.
 61. The CAR of any oneof claims 1-59, wherein the extracellular antigen-binding domain bindsto an epitope comprising the amino acid sequence set forth in SEQ IDNO:965.
 62. The CAR of any one of claims 1-61, wherein the transmembranedomain comprises a CD8 polypeptide, a CD28 polypeptide, a CD3ζpolypeptide, a CD4 polypeptide, a 4-1BB polypeptide, an OX40polypeptide, an ICOS polypeptide, a CTLA-4 polypeptide, a PD-1polypeptide, a LAG-3 polypeptide, a 2B4 polypeptide, a BTLA polypeptide,a synthetic peptide (not based on a protein associated with the immuneresponse), or a combination thereof.
 63. The CAR of any one of claims1-62, wherein the transmembrane domain comprises a CD8 polypeptide. 64.The CAR of any one of claims 1-62, wherein the transmembrane domaincomprises a CD28 polypeptide.
 65. The CAR of any one of claims 1-62,wherein the intracellular domain comprises a CD3ζ polypeptide.
 66. TheCAR of any one of claims 1-65, wherein the intracellular domain furthercomprises at least one signaling region.
 67. The CAR of claim 66,wherein the at least one signaling region comprises a CD28 polypeptide,a 4-1BB polypeptide, an OX40 polypeptide, an ICOS polypeptide, a PD-1polypeptide, a CTLA-4 polypeptide, a LAG-3 polypeptide, a 2B4polypeptide, a BTLA polypeptide, a synthetic peptide (not based on aprotein associated with the immune response), or a combination thereof.68. CAR of claim 66 or 67, wherein the signaling region is aco-stimulatory signaling region.
 69. The CAR of claim 68, wherein the atleast one co-stimulatory signaling region comprises a CD28 polypeptide,a 4-1BB polypeptide, an OX40 polypeptide, an ICOS polypeptide, a DAP-10polypeptide, or a combination thereof.
 70. The CAR of claim 68, whereinthe at least one co-stimulatory signaling region comprises a CD28polypeptide.
 71. The CAR of any one of claims 1-62, wherein thetransmembrane domain comprises a CD28 polypeptide, the intracellulardomain comprises a CD3ζ polypeptide, and the co-stimulatory signalingdomain comprises a CD28 polypeptide.
 72. The CAR of any one of claims1-62, wherein the transmembrane domain comprises a CD8 polypeptide, theintracellular domain comprises a CD3ζ polypeptide, and theco-stimulatory signaling domain comprises a 4-1BB polypeptide.
 73. TheCAR of any one of claims 1-72, wherein the CAR is recombinantlyexpressed.
 74. The CAR of any one of claims 1-73, wherein the CAR isexpressed from a vector.
 75. The CAR of claim 74, wherein the vector isa γ-retroviral rector.
 76. An isolated immunoresponsive cell comprisingthe CAR of any one of the preceding claims.
 77. The isolatedimmunoresponsive cell of claim 76, wherein the immunoresponsive cell istransduced with the CAR.
 78. The isolated immunoresponsive cell of claim76 or 77, wherein the CAR is constitutively expressed on the surface ofthe immunoresponsive cell.
 79. The isolated immunoresponsive cell of anyone of claims 76-78, wherein the isolated immunoresponsive cell isfurther transduced with at least one co-stimulatory ligand such that theimmunoresponsive cell expresses the at least one co-stimulatory ligand.80. The isolated immunoresponsive cell of claim 79, wherein the at leastone co-stimulatory ligand is selected from the group consisting of4-1BBL, CD80, CD86, CD70, OX40L, CD48, TNFRSF14, and combinationsthereof.
 81. The isolated immunoresponsive cell of any one of claims76-80, wherein the isolated immunoresponsive cell is further transducedwith at least one cytokine such that the immunoresponsive cell secretsthe at least one cytokine.
 82. The isolated immunoresponsive cell ofclaim 81, wherein the at least one cytokine is selected from the groupconsisting of IL-2, IL-3, IL-6, IL-7, IL-11, IL-12, IL-15, IL-17, IL-21,and combinations thereof.
 83. The isolated immunoresponsive cell of anyone of claims 76-82, wherein the immunoresponsive cell is selected fromthe group consisting of a T cell, a Natural Killer (NK) cell, acytotoxic T lymphocyte (CTL), a regulatory T cell, a human embryonicstem cell, a lymphoid progenitor cell, a T cell-precursor cell, and apluripotent stem cell from which lymphoid cells may be differentiated.84. The isolated immunoresponsive cell of claim 83, wherein theimmunoresponsive cell is a T cell.
 85. An isolated nucleic acid moleculeencoding the chimeric antigen receptor (CAR) of any one of claims 1-75.86. The isolated nucleic acid molecule of claim 85, comprising a nucleicacid selected from the group consisting of SEQ ID NOs:951-959.
 87. Theisolated nucleic acid sequence of claim 85, comprising nucleic acidshaving the sequence set forth in SEQ ID NO:951.
 88. The isolated nucleicacid sequence of claim 85, comprising nucleic acids having the sequenceset forth in SEQ ID NO:952.
 89. The isolated nucleic acid sequence ofclaim 85, comprising nucleic acids having the sequence set forth in SEQID NO:953.
 90. The isolated nucleic acid sequence of claim 85,comprising nucleic acids having the sequence set forth in SEQ ID NO:954.91. The isolated nucleic acid sequence of claim 85, comprising nucleicacids having the sequence set forth in SEQ ID NO:955.
 92. The isolatednucleic acid sequence of claim 85, comprising nucleic acids having thesequence set forth in SEQ ID NO:956.
 93. The isolated nucleic acidsequence of claim 85, comprising nucleic acids having the sequence setforth in SEQ ID NO:957.
 94. The isolated nucleic acid sequence of claim85, comprising nucleic acids having the sequence set forth in SEQ IDNO:958.
 95. The isolated nucleic acid sequence of claim 85, comprisingnucleic acids having the sequence set forth in SEQ ID NO:959.
 96. Avector comprising the isolated nucleic acid molecule of any one ofclaims 85-95.
 97. The vector of claim 96, wherein the vector is aγ-retroviral rector.
 98. A host cell expressing the nucleic acidmolecule of any one of claims 85-95.
 99. The host cell of claim 98,wherein the host cell is a T cell.
 100. A method of reducing tumorburden in a subject, comprising administering an effective amount of theimmunoresponsive cell of any one of claims 76-84 to the subject, therebyinducing tumor cell death in the subject.
 101. The method of claim 100,wherein the method reduces the number of tumor cells.
 102. The method ofclaim 100, wherein the method reduces tumor size.
 103. The method ofclaim 100, wherein the method eradicates the tumor in the subject. 104.The method of any one of claims 100-103, wherein the tumor is selectedfrom the group consisting of multiple myeloma, Non-Hodgkin Lymphoma(especially Mantle Cell), Hodgkin Lymphoma, Chronic Lymphocytic Leukemia(CLL), Acute lymphocytic leukemia (ALL), Hairy Cell Leukemia, BurkettsLymphoma, and Waldenstrom's Macroglobulinemia.
 105. The method of anyone of claims 100-104, wherein the tumor is multiple myeloma.
 106. Themethod of any one of claims 100-105, wherein the subject is a human.107. The method of any one of claims 100-106, wherein theimmunoresponsive cell is a T cell.
 108. A method of increasing orlengthening survival of a subject having neoplasia, comprisingadministering an effective amount of the immunoresponsive cell of anyone of claims 76-84 to the subject, thereby increasing or lengtheningsurvival of the subject.
 109. The method of claim 108, wherein theneoplasia is selected from the group consisting of multiple myeloma,Non-Hodgkin Lymphoma (especially Mantle Cell), Hodgkin Lymphoma, ChronicLymphocytic Leukemia (CLL), Acute lymphocytic leukemia (ALL), Hairy CellLeukemia, Burketts Lymphoma, and Waldenstrom's Macroglobulinemia. 110.The method of claim 108 or 109, wherein the neoplasia is multiplemyeloma.
 111. The method of any one of claims 108-110, wherein themethod reduces or eradicates tumor burden in the subject.
 112. A methodfor producing an immunoresponsive cell that binds to Fc Receptor-like 5(FcRL5), comprising introducing into the immunoresponsive cell a nucleicacid sequence that encodes a chimeric antigen receptor (CAR) comprisingan extracellular antigen-binding domain, a transmembrane domain and anintracellular domain, wherein the extracellular antigen-binding domainthat specifically binds to FcRL5.
 113. A pharmaceutical compositioncomprising an effective amount of the immunoresponsive cell of any oneof claims 76-84 and a pharmaceutically acceptable excipient.
 114. Thepharmaceutical composition of claim 113, wherein the pharmaceuticalcomposition is for treating a neoplasia.
 115. The pharmaceuticalcomposition of claim 114, wherein the neoplasia is selected from thegroup consisting of multiple myeloma, Non-Hodgkin Lymphoma (especiallyMantle Cell), Hodgkin Lymphoma, Chronic Lymphocytic Leukemia (CLL),Acute lymphocytic leukemia (ALL), Hairy Cell Leukemia, BurkettsLymphoma, and Waldenstrom's Macroglobulinemia.
 116. The pharmaceuticalcomposition of claim 113, 114 or 115, wherein the neoplasia is multiplemyeloma.
 117. A kit for treating a neoplasia, comprising theimmunoresponsive cell of any one of claims 76-84.
 118. The kit of claim117, wherein the kit further comprises written instructions for usingthe immunoresponsive cell for treating a subject having a neoplasia.119. The kit of claim 117 or 118, wherein the neoplasia is selected fromthe group consisting of multiple myeloma, Non-Hodgkin Lymphoma(especially Mantle Cell), Hodgkin Lymphoma, Chronic Lymphocytic Leukemia(CLL), Acute lymphocytic leukemia (ALL), Hairy Cell Leukemia, BurkettsLymphoma, and Waldenstrom's Macroglobulinemia.
 120. The kit of claim117, 118 or 119, wherein the neoplasia is multiple myeloma.